Autism Speaks now saying that there is more evidence of microglial activation in Autism

[Guest guest]

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Autism Speaks completely ignored the request from hundreds of parents asking to fund a treatment to address microglial activation in autism http://autismspeaks.ideascale.com/a/dtd/Evaluation-of-the-SCIA-Treatment-Protocol-in-Children-with-ASD/94485-15895 Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123 From: Stop Calling It Autism! Sent: Tuesday, January 08, 2013 9:49 PMTo: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Subject: Autism Speaks now saying that there is more evidence of microglial activation in Autism Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

autism speaks is a joke. To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:57 PM Subject: RE: Autism Speaks now saying that there is more evidence of

microglial activation in Autism

Autism Speaks completely ignored the request from hundreds of parents asking to fund a treatment to address microglial activation in autism http://autismspeaks.ideascale.com/a/dtd/Evaluation-of-the-SCIA-Treatment-Protocol-in-Children-with-ASD/94485-15895 Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123 From: Stop Calling It Autism! Sent: Tuesday, January 08, 2013 9:49 PMTo: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Subject: Autism Speaks now saying that there is more evidence of microglial activation in Autism Go figure... That Autism Speaks denied us several requests for a grant for a

treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

why do you say so?Ive been going through there stuff and I am still trying to understand but my thing is that He has an assosiation with Dr Goldberg.This is why I think there might be something here, that could help some children i am not saying all ..but im in the Uk so I might not be as up to date as yourself over there.Oh how I wish WE knew for sure...Bola To: mb12valtrex From: brooke0618@...Date: Tue, 8 Jan 2013 21:42:42 -0800Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

autism speaks is a joke. To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:57 PM Subject: RE: Autism Speaks now saying that there is more evidence of

microglial activation in Autism

Autism Speaks completely ignored the request from hundreds of parents asking to fund a treatment to address microglial activation in autism http://autismspeaks.ideascale.com/a/dtd/Evaluation-of-the-SCIA-Treatment-Protocol-in-Children-with-ASD/94485-15895 Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123 From: Stop Calling It Autism! Sent: Tuesday, January 08, 2013 9:49 PMTo: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Subject: Autism Speaks now saying that there is more evidence of microglial activation in Autism Go figure... That Autism Speaks denied us several requests for a grant for a

treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Autism speaks doesnt fund anything to find the cause.Quite frankly id love to know what they do fund.Heres what made me say see ya.I watched the Dr Drew show last year and i see the old president of autism speaks say vaccines have nothing to do with autism.He believed it was genetic.Meanwhile,im giving them money in my daughters name.Funny thing is autism speaks started because of s son who shes stated herself vaccines caused her sons autism.Autism speaks last i checked doesnt promote anything we talk about in these groups.Although seems lately there inching at it.I encourage you to read mother warriors by McCarthy.A great explanation there.Its no wonder our govt supports autism speaks.Places like generation rescue,taca,and SCIA are trying to find the real cause.Autism speaks is known for their

passionate love for vaccines and thats a joke. To: "mb12valtrex " <mb12valtrex > Sent: Wednesday, January 9, 2013 7:32 AM Subject: RE: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

why do you say so?Ive been going through there stuff and I am still trying to understand but my thing is that He has an assosiation with Dr Goldberg.Th vis is why I think there might be something here, that could help some children i am not saying all ..but im in the Uk so I might not be as up to date as yourself over there.Oh how I wish WE knew for sure...Bola To: mb12valtrex From: brooke0618@... autism Date: Tue, 8 Jan 2013 21:42:42 -0800Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

autism speaks is a joke. To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:57 PM Subject: RE: Autism Speaks now saying that there is more evidence of

microglial activation in Autism

Autism Speaks completely ignored the request from hundreds of parents asking to fund a treatment to address microglial activation in autism http://autismspeaks.ideascale.com/a/dtd/Evaluation-of-the-SCIA-Treatment-Protocol-in-Children-with-ASD/94485-15895 Thanks, Founder and Director of Stop

Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123 From: Stop Calling It Autism! Sent: Tuesday, January 08, 2013 9:49 PMTo: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Subject: Autism Speaks now saying that there is more evidence of microglial activation

in Autism Go figure... That Autism Speaks denied us several requests for a grant for a

treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: (888)

724-2123 or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Maybe your confused.I love SCIA.Im a member of there yahoo group.SCIA started the microlial activation studies.I dont like autism speaks.Two different organizations.I got an e mail earlier saying autism speaks wont fund microglial activation.Now there saying more evidence.Thats great im thrilled autism speaks has got some sense.I would never not support something to help kids.Im very interested to see where this goes! To: "mb12valtrex " <mb12valtrex > Sent: Wednesday, January 9, 2013 7:32 AM Subject: RE: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

why do you say so?Ive been going through there stuff and I am still trying to understand but my thing is that He has an assosiation with Dr Goldberg.This is why I think there might be something here, that could help some children i am not saying all ..but im in the Uk so I might not be as up to date as yourself over there.Oh how I wish WE knew for sure...Bola To: mb12valtrex From: brooke0618@...Date: Tue, 8 Jan 2013 21:42:42 -0800Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

autism speaks is a joke. To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:57 PM Subject: RE: Autism Speaks now saying that there is more evidence of

microglial activation in Autism

Autism Speaks completely ignored the request from hundreds of parents asking to fund a treatment to address microglial activation in autism http://autismspeaks.ideascale.com/a/dtd/Evaluation-of-the-SCIA-Treatment-Protocol-in-Children-with-ASD/94485-15895 Thanks, Founder and Director of Stop

Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123 From: Stop Calling It Autism! Sent: Tuesday, January 08, 2013 9:49 PMTo: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Subject: Autism Speaks now saying that there is more evidence of microglial activation

in Autism Go figure... That Autism Speaks denied us several requests for a grant for a

treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: (888)

724-2123 or (888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

----- Forwarded Message ----- To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:49 PM Subject: Autism Speaks now saying that there is more evidence of microglial activation

in Autism

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or

(888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Autism Leeches looking for a bandwagon to jump on and justify their overhead spending.Sent from my iPhone

----- Forwarded Message ----- To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:49 PM Subject: Autism Speaks now saying that there is more evidence of microglial activation

in Autism

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or

(888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Exactly.Now theyll take credit To: "mb12valtrex " <mb12valtrex > Sent: Wednesday, January 9, 2013 2:17 PM Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

Autism Leeches looking for a bandwagon to jump on and justify their overhead spending.Sent from my iPhone

----- Forwarded Message ----- To: stopcallingitautism ; stopcallingitautismfordoctors ; mb12valtrex ; GFCFKids Sent: Tuesday, January 8, 2013 10:49 PM Subject: Autism Speaks now saying that there is more evidence of microglial activation

in Autism

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or

(888) SCIA-123SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.htmlSCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautismSCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautismSCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanolSCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

Thats okay Bola Autism Speaks confuses everyone lol.Im the SAME way w/brainfog and memory.Alot of parents it seems of ASD children have these issues.Thanks for your reply.Have a good day! To: mb12valtrex Sent: Wednesday, January 9, 2013 11:13 PM Subject: RE: RE: Autism Speaks now

saying that there is more evidence of microglial activation in Autism

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

I believe 90% of the human population has brain fog and just not aware of it Sent from my iPhone

Thats okay Bola Autism Speaks confuses everyone lol.Im the SAME way w/brainfog and memory.Alot of parents it seems of ASD children have these issues.Thanks for your reply.Have a good day! To: mb12valtrex Sent: Wednesday, January 9, 2013 11:13 PM Subject: RE: RE: Autism Speaks now

saying that there is more evidence of microglial activation in Autism

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

especially the medical establishment! To: "mb12valtrex " <mb12valtrex > Sent: Thursday, January 10, 2013 12:47 PM Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

I believe 90% of the human population has brain fog and just not aware of it Sent from my iPhone

Thats okay Bola Autism Speaks confuses everyone lol.Im the SAME way w/brainfog and memory.Alot of parents it seems of ASD children have these issues.Thanks for your reply.Have a good day! To: mb12valtrex Sent: Wednesday, January 9, 2013 11:13 PM Subject: RE: RE: Autism Speaks now

saying that there is more evidence of microglial activation in Autism

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

To: mb12valtrex From: tendaimatambanadzo@...Date: Thu, 10 Jan 2013 17:47:41 +0000Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

I believe 90% of the human population has brain fog and just not aware of it Sent from my iPhone

Thats okay Bola Autism Speaks confuses everyone lol.Im the SAME way w/brainfog and memory.Alot of parents it seems of ASD children have these issues.Thanks for your reply.Have a good day! To: mb12valtrex Sent: Wednesday, January 9, 2013 11:13 PM Subject: RE: RE: Autism Speaks now

saying that there is more evidence of microglial activation in Autism

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

E-mailPrint Share This

Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,†notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.â€

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,†Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,†Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,†Kipnis says, “but it’s not meaningful enough.â€

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism

SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol

SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

E-mailPrint Share This

Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,” notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.”

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,” Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,” Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,” Kipnis says, “but it’s not meaningful enough.”

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Hear hearSent from my iPhone

especially the medical establishment! To: "mb12valtrex " <mb12valtrex > Sent: Thursday, January 10, 2013 12:47 PM Subject: Re: RE: Autism Speaks now saying that there is more evidence of microglial activation in Autism

I believe 90% of the human population has brain fog and just not aware of it Sent from my iPhone

Thats okay Bola Autism Speaks confuses everyone lol.Im the SAME way w/brainfog and memory.Alot of parents it seems of ASD children have these issues.Thanks for your reply.Have a good day! To: mb12valtrex Sent: Wednesday, January 9, 2013 11:13 PM Subject: RE: RE: Autism Speaks now

saying that there is more evidence of microglial activation in Autism

sorry your right I read it wrong .Its because I know that your into everything positive that I asked the question .Its another brain fog day (sigh)lolBola

[Guest guest]

Yes the article says that it is confusing because they are also needed for a healthy brain. Maybe it makes a difference what causes the activation. If it is the immune system or if it is the healthy activity? Sent from my iPhone

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

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Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,†notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.â€

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,†Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,†Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,†Kipnis says, “but it’s not meaningful enough.â€

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

They are saying the microglia, the cells reponsible for brains immunity, are over activated leading to neurotoxicity and neurodegeneration. Not just activated. A variety of MI have been linked to overactive micoglia. Also Parkinsons has been linked to microglia over actvation.

Watch this:

http://www.youtube.com/watch?v=S4EzJXZrnP0

http://www.ksl.com/?nid=148 & sid=10947928 (longer interview here)

read this:

Molecular mechanisms: Microglia abnormal in autism brains

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Popularity tracker

5 June 2012

Treating tentacles: More microglia (brown) wrap around the cell bodies of neurons (purple) in the brains of individuals with autism (both panels, above) than in controls.

Two new postmortem studies show that microglia, which protect the brain from invaders, are denser and more concentrated around neurons in the brains of individuals with autism than in those of controls1,2.

Microglia are the immune molecules of the brain, engulfing invading molecules via constantly moving tentacles. Originally thought to merely support neurons, they have since been shown to play more central roles in the brain.

Microglia are located near synapses, the junctions between neurons. More microglia appear around synapses after mice are deprived of light, suggesting that they may be involved in pruning neuronal connections.

A study published in March showed that a bone marrow transplant alleviates most symptoms of Rett syndrome in a mouse model, perhaps by generating healthy microglia.

Postmortem studies have found abnormal microglia in the brains of individuals with autism. For example, a 2010 study showed that 5 of 13 postmortem autism brains have enlarged microglia that are likely to be active in immune function.

The first new study, published 31 March in the Journal of Autism and Developmental Disorders, compared 10 autism brains and 12 control brains. It found that microglia are about 20 percent more dense in two regions of the cerebral cortex, a brain region involved in higher-level cognition, in the autism brains. The researchers presented the preliminary results at the 2009 Society for Neuroscience annual meeting in Chicago.

The second study, published last week in Brain Research, looked at microglia in the prefrontal cortex of 13 autism brains and 9 controls. The microglia are denser at 25, 75 and 100 micrometers away from neurons in the autism brains compared with controls, the study found. For example, at 25 micrometers from neurons, where the microglia are most dense in autism brains, there is a 12 increase in density compared with controls.

The microglia are denser than in controls even at 50 micrometers, but this result is not statistically significant. This could be because microglia at this distance are propelled to move even closer to neurons, accounting for the greater increase at 25 micrometers, the researchers say.

The researchers found that three autism brains from children younger than 6 years also have more microglia surrounding neurons when compared with two age-matched controls. This suggests that interactions between microglia and neurons could be a cause and not just a consequence of autism, the researchers say.

The link between abnormal microglia and autism is still unclear. One possibility is that an underlying immune condition activates microglia, which then target neurons and disrupt neuronal connections. Studies have shown that mothers who have antibodies against brain proteins are more likely than controls to have children with autism.

Another possibility is that a mutation affects the microglia directly, causing them to be overactive. This is the case in Nasu-Hakola disease, which causes silly behavior, social inhibition and ultimately dementia.

References:

1: Tetreault N.A. et al. J. Autism Dev. Disord. Epub ahead of print (2012) PubMed

2: J.T. et al. Brain Res. 1456, 72-81 (2012) PubMed

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

The microglia are overactivated. they also appear shriveled and damaged in post mortem brain tissue of children with autism meaning may cause abnormal signaling.

See photo of microglia here in a child with autism vs a typical child

http://sfari.org/news-and-opinion/in-brief/2010/molecular-mechanisms-autism-brains-show-activated-immune-defense?searchterm=angry+microglia%2C+autism

Scientists capture microglia's role in brain connectivity

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Popularity tracker

Virginia

20 December 2010

PLoS Biol.

Pruning partners: After mice are left for days in the dark (top), their microglia (black) are more likely to engulf parts of the synapse (pink) than are those of mice re-exposed to light (above).

Scientists are changing their minds about the role of microglia, the brain's strongest and most agile soldiers against damage and infection.

Microglia are versatile beyond the immune system, and could be important for neurological disorders, including autism, according to a study published 2 November in PLoS Biology1.

Using high-tech imaging, the researchers captured dynamic, ongoing interactions between microglia and synapses — the junctions between neurons — showing that, in healthy brains, microglia help build and eliminate synapses.

"Our work suggests that these cells are not just sitting around waiting for something horrible to happen to the brain. They're actually doing important things all the time to help with brain function, and synaptic function in particular," notes lead investigator Ania Majewska, assistant professor of neurobiology and anatomy at the University of Rochester in New York.

This influence on brain connectivity could explain why microglia keep popping up in studies of cognitive disorders ranging from Alzheimer's and Parkinson's diseases to Rett syndrome and autism. In 1990, Graeber, chair of brain tumor research at the University of Sydney in Australia, first proposed that microglia are the main component of the brain's 'immune network2.' At the time, most people thought that the cells are usually at rest, dramatically changing shape in the presence of an infection and engulfing foreign particles.

In 2005, however, a German team discovered that the term 'resting microglia' is an oxymoron: the cells' branches are in fact continually reaching out to their cellular neighbors — acting, as the researchers put it, like "busy and vigilant housekeepers3."

"Their little processes are zipping away all over the place," Majewska says. Her new study suggests that this activity is much more than an infection patrol.

Her team took close-up pictures and videos of microglia in the visual cortex of young mice. They chose this region partly because its activity can be probed simply by changing light conditions.

One method, called two-photon imaging, captures the interactions of cells in live mice. By genetically engineering the mice so that microglia glow yellow and neurons green, the researchers could watch the cells dancing together in real time.

Using electron microscopy — which gives a high-resolution picture of fixed tissue — the researchers found that microglia touch and wrap around several parts of the synapse. In animals that had been deprived of light for about a week, microglia are larger and have more of these interactions with the synaptic cleft, the tiny gap between two neurons.

What's more, in mice exposed to darkness, microglia are more likely to have engulfed parts of the synapse, suggesting that the cells are helping the brain adapt by pruning unnecessary connections.

"This paper is a breakthrough in that it really demonstrates that microglia respond to experience," Graeber says.

The findings align with a perspective he published 5 November in Science4, in which he proposed that, more than soldiers or housekeepers, microglia are like electricians: maintaining and installing electrical equipment from outside the circuit.

Autism activation:

Microglia have been a hot topic in the autism field since 2005, when a group led by Pardo identified activated microglia and inflammation in postmortem brain tissue from children with autism5.

In August, Pardo and colleagues looked at the structure of microglia in much more detail. They again found an abundance of activated microglia in autistic brains, and showed that the cells are larger and denser6.

Because of microglia's reputation as infection-fighters, these reports have fueled speculation that the immune system is disrupted in people with autism. But the new work shows that microglial shape-shifting happens all the time, and not necessarily as a marker of immune response.

Using a sophisticated imaging technique, researchers visualized the intricate interactions between neurons (green) and microglia (yellow).

"We still don't have a good explanation for why microglia are activated in autism," says Pardo, associate professor of neurology and pathology at s Hopkins University in Baltimore. "It could be because there is a protective factor, or it could be in response to synaptic abnormalities. We just don't know."

Clarifying the role of these cells in autism could lead to a new class of treatments. Because microglia operate independently of neurons, drugs might be targeted to microglia without affecting cell circuitry. "Microglia are more amenable to therapy than neurons," notes Lee-Way Jin, associate professor of pathology at the M.I.N.D. Institute at the University of California, .

For a study published earlier this year, Jin and collaborator Izumi Maezawa harvested microglia from healthy mice and those missing MeCP2, the gene that causes Rett syndrome. Looking in cultured cells, they found that in the presence of the mutant microglia, neurons grow with stunted dendrites, the long projections that receive electric signals7.

Jin is developing a drug that blocks a potassium channel that is specific to microglia. Targeting the channel might allow researchers to regulate the action of the microglia. "But we have to walk a fine line — we want to inhibit microglia activation, but also preserve its beneficial effects."

References:

Tremblay M.È. et al. PLoS Biol. 8, e1000527 (2010) PubMed

Graeber M.B. and W.J. Streit Brain Pathol. 1, 2-5 (1990) PubMed

> wrote:

Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "mb12valtrex " <mb12valtrex >Date: Friday, January 11, 2013, 6:45 AM

Yes the article says that it is confusing because they are also needed for a healthy brain. Maybe it makes a difference what causes the activation. If it is the immune system or if it is the healthy activity?

Sent from my iPhone

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

E-mailPrint Share This

Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,†notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.â€

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,†Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,†Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,†Kipnis says, “but it’s not meaningful enough.â€

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism

SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol

SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Here's another study:

Microglial Activation in Young Adults With Autism Spectrum Disorder

Katsuaki Suzuki, MD, PhD; Genichi Sugihara, MD, PhD; Yasuomi Ouchi, MD, PhD; Kazuhiko Nakamura, MD, PhD; Masami Futatsubashi, BS; Kiyokazu Takebayashi, MD, PhD; Yujiro Yoshihara, MD, PhD; Kei Omata, PhD; Kaori Matsumoto, MA; Kenji J. Tsuchiya, MD, PhD; Yasuhide Iwata, MD, PhD; Masatsugu Tsujii, MA; Toshirou Sugiyama, MD, PhD; Norio Mori, MD, PhD JAMA Psychiatry. 2013;70(1):49-58. doi:10.1001/jamapsychiatry.2013.272.

Published online

ABSTRACT

Context A growing body of evidence suggests that aberrant immunologic systems underlie the pathophysiologic characteristics of autism spectrum disorder (ASD). However, to our knowledge, no information is available on the patterns of distribution of microglial activation in the brain in ASD.

Objectives To identify brain regions associated with excessively activated microglia in the whole brain, and to examine similarities in the pattern of distribution of activated microglia in subjects with ASD and control subjects.

Design Case-control study using positron emission tomography and a radiotracer for microglia—[11C]®-(1-[2-chrorophynyl]- N-methyl- N-[1-methylpropyl]-3 isoquinoline carboxamide) ([11C]®-PK11195).

Setting Subjects recruited from the community.

Participants Twenty men with ASD (age range, 18-31 years; mean [sD] IQ, 95.9 [16.7]) and 20 age- and IQ-matched healthy men as controls. Diagnosis of ASD was made in accordance with the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised.

Main Outcome Measures Regional brain [11C]®-PK11195 binding potential as a representative measure of microglial activation.

Results The [11C]®-PK11195 binding potential values were significantly higher in multiple brain regions in young adults with ASD compared with those of controls (P < .05, corrected). Brain regions with increased binding potentials included the cerebellum, midbrain, pons, fusiform gyri, and the anterior cingulate and orbitofrontal cortices. The most prominent increase was observed in the cerebellum. The pattern of distribution of [11C]®-PK11195 binding potential values in these brain regions of ASD and control subjects was similar, whereas the magnitude of the [11C]®-PK11195 binding potential in the ASD group was greater than that of controls in all regions.

Conclusions Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD. The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD.

Figures in this Article

http://archpsyc.jamanetwork.com/article.aspx?articleid=1393597

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism

SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol

SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

Yes this could be the case - what does over-activated actually mean though - what part of their molecular structure is high To: mb12valtrex From: sailcharters@...Date: Fri, 11 Jan 2013 04:57:19 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The microglia are overactivated. they also appear shriveled and damaged in post mortem brain tissue of children with autism meaning may cause abnormal signaling.

See photo of microglia here in a child with autism vs a typical child

http://sfari.org/news-and-opinion/in-brief/2010/molecular-mechanisms-autism-brains-show-activated-immune-defense?searchterm=angry+microglia%2C+autism

Scientists capture microglia's role in brain connectivity

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Popularity tracker

Virginia

20 December 2010

PLoS Biol.

Pruning partners: After mice are left for days in the dark (top), their microglia (black) are more likely to engulf parts of the synapse (pink) than are those of mice re-exposed to light (above).

Scientists are changing their minds about the role of microglia, the brain's strongest and most agile soldiers against damage and infection.

Microglia are versatile beyond the immune system, and could be important for neurological disorders, including autism, according to a study published 2 November in PLoS Biology1.

Using high-tech imaging, the researchers captured dynamic, ongoing interactions between microglia and synapses — the junctions between neurons — showing that, in healthy brains, microglia help build and eliminate synapses.

"Our work suggests that these cells are not just sitting around waiting for something horrible to happen to the brain. They're actually doing important things all the time to help with brain function, and synaptic function in particular," notes lead investigator Ania Majewska, assistant professor of neurobiology and anatomy at the University of Rochester in New York.

This influence on brain connectivity could explain why microglia keep popping up in studies of cognitive disorders ranging from Alzheimer's and Parkinson's diseases to Rett syndrome and autism. In 1990, Graeber, chair of brain tumor research at the University of Sydney in Australia, first proposed that microglia are the main component of the brain's 'immune network2.' At the time, most people thought that the cells are usually at rest, dramatically changing shape in the presence of an infection and engulfing foreign particles.

In 2005, however, a German team discovered that the term 'resting microglia' is an oxymoron: the cells' branches are in fact continually reaching out to their cellular neighbors — acting, as the researchers put it, like "busy and vigilant housekeepers3."

"Their little processes are zipping away all over the place," Majewska says. Her new study suggests that this activity is much more than an infection patrol.

Her team took close-up pictures and videos of microglia in the visual cortex of young mice. They chose this region partly because its activity can be probed simply by changing light conditions.

One method, called two-photon imaging, captures the interactions of cells in live mice. By genetically engineering the mice so that microglia glow yellow and neurons green, the researchers could watch the cells dancing together in real time.

Using electron microscopy — which gives a high-resolution picture of fixed tissue — the researchers found that microglia touch and wrap around several parts of the synapse. In animals that had been deprived of light for about a week, microglia are larger and have more of these interactions with the synaptic cleft, the tiny gap between two neurons.

What's more, in mice exposed to darkness, microglia are more likely to have engulfed parts of the synapse, suggesting that the cells are helping the brain adapt by pruning unnecessary connections.

"This paper is a breakthrough in that it really demonstrates that microglia respond to experience," Graeber says.

The findings align with a perspective he published 5 November in Science4, in which he proposed that, more than soldiers or housekeepers, microglia are like electricians: maintaining and installing electrical equipment from outside the circuit.

Autism activation:

Microglia have been a hot topic in the autism field since 2005, when a group led by Pardo identified activated microglia and inflammation in postmortem brain tissue from children with autism5.

In August, Pardo and colleagues looked at the structure of microglia in much more detail. They again found an abundance of activated microglia in autistic brains, and showed that the cells are larger and denser6.

Because of microglia's reputation as infection-fighters, these reports have fueled speculation that the immune system is disrupted in people with autism. But the new work shows that microglial shape-shifting happens all the time, and not necessarily as a marker of immune response.

Using a sophisticated imaging technique, researchers visualized the intricate interactions between neurons (green) and microglia (yellow).

"We still don't have a good explanation for why microglia are activated in autism," says Pardo, associate professor of neurology and pathology at s Hopkins University in Baltimore. "It could be because there is a protective factor, or it could be in response to synaptic abnormalities. We just don't know."

Clarifying the role of these cells in autism could lead to a new class of treatments. Because microglia operate independently of neurons, drugs might be targeted to microglia without affecting cell circuitry. "Microglia are more amenable to therapy than neurons," notes Lee-Way Jin, associate professor of pathology at the M.I.N.D. Institute at the University of California, .

For a study published earlier this year, Jin and collaborator Izumi Maezawa harvested microglia from healthy mice and those missing MeCP2, the gene that causes Rett syndrome. Looking in cultured cells, they found that in the presence of the mutant microglia, neurons grow with stunted dendrites, the long projections that receive electric signals7.

Jin is developing a drug that blocks a potassium channel that is specific to microglia. Targeting the channel might allow researchers to regulate the action of the microglia. "But we have to walk a fine line — we want to inhibit microglia activation, but also preserve its beneficial effects."

References:

Tremblay M.È. et al. PLoS Biol. 8, e1000527 (2010) PubMed

Graeber M.B. and W.J. Streit Brain Pathol. 1, 2-5 (1990) PubMed

> wrote:

Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "mb12valtrex " <mb12valtrex >Date: Friday, January 11, 2013, 6:45 AM

Yes the article says that it is confusing because they are also needed for a healthy brain. Maybe it makes a difference what causes the activation. If it is the immune system or if it is the healthy activity?

Sent from my iPhone

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

E-mailPrint Share This

Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,” notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.”

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,” Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,” Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,” Kipnis says, “but it’s not meaningful enough.”

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

These studies may shed some light..

Nat Neurosci. 2006 Jul;9(7):917-24. Epub 2006 Jun 18.

Control of microglial neurotoxicity by the fractalkine receptor.

Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S,

Lira SA, Littman DR, Ransohoff RM.

Source

Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland, Ohio 44195, USA.

Abstract

Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

http://www.ncbi.nlm.nih.gov/pubmed/16732273

Role of fractalkine (CX3CL1) in regulating neuron-microglia interactions: development of viral-based CX3CR1 antagonists.

Streit WJ, CN, on JK.

Source

Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA. streit@...

Abstract

Blocking the effects of fractalkine therapeutically may regulate microglia cell activation and provide neuroprotection in the AD brain. A human herpesvirus 8-encoded chemokine, termed vMIP-II is a non-selective chemokine receptor antagonist (binding multiple chemokine receptors, including CX3CR1). By comparing vMIP-II and FKN, we have generated molecules that selectively antagonize CX3CR1 activation. The results from these studies will guide future development of therapeutic agents designed to modulate microglial activation with the goal of preventing or slowing the progression of AD.

http://www.ncbi.nlm.nih.gov/pubmed/15974917

Fractalkine receptor (CX3CR1) deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide

W Corona1*, Yan Huang1, C O'Connor2,6, Dantzer2, W Kelley2, G Popovich3,4,5 and

P Godbout1,3,4,5*

* Corresponding authors: W Corona .Wynne@... - P Godbout .Godbout@...

Author Affiliations

1 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA

2 Department of Animal Science, University of Illinois, 1201 W. Drive, 250B R. Madigan Laboratory, Urbana, IL 61820, USA

3 Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Dr., Columbus, OH 43210, USA

4 Center for Brain and Spinal Cord Repair, The Ohio State University, 460 W. 12th Ave, Columbus, OH 43210, USA

5 Department of Neuroscience, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA

6 Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San , TX 78229, USA

For all author emails, please log on.

Journal of Neuroinflammation 2010, 7:93 doi:10.1186/1742-2094-7-93

The electronic version of this article is the complete one and can be found online at: http://www.jneuroinflammation.com/content/7/1/93

Received:

18 October 2010

Accepted:

17 December 2010

Published:

17 December 2010

© 2010 Corona et al.; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Interactions between fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) regulate microglial activation in the CNS. Recent findings indicate that age-associated impairments in CX3CL1 and CX3CR1 are directly associated with exaggerated microglial activation and an impaired recovery from sickness behavior after peripheral injection of lipopolysaccharide (LPS). Therefore, the purpose of this study was to determine the extent to which an acute LPS injection causes amplified and prolonged microglial activation and behavioral deficits in CX3CR1-deficient mice (CX3CR1-/-).

Methods

CX3CR1-/- mice or control heterozygote mice (CX3CR1+/-) were injected with LPS (0.5 mg/kg i.p.) or saline and behavior (i.e., sickness and depression-like behavior), microglial activation, and markers of tryptophan metabolism were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions.

Results

LPS injection caused a prolonged duration of social withdrawal in CX3CR1-/- mice compared to control mice. This extended social withdrawal was associated with enhanced mRNA expression of IL-1β, indolamine 2,3-dioxygenase (IDO) and kynurenine monooxygenase (KMO) in microglia 4 h after LPS. Moreover, elevated expression of IL-1β and CD14 was still detected in microglia of CX3CR1-/- mice 24 h after LPS. There was also increased turnover of tryptophan, serotonin, and dopamine in the brain 24 h after LPS, but these increases were independent of CX3CR1 expression. When submitted to the tail suspension test 48 and 72 h after LPS, an increased duration of immobility was evident only in CX3CR1-/- mice. This depression-like behavior in CX3CR1-/- mice was associated with a persistent activated microglial phenotype in the hippocampus and

prefrontal cortex. Conclusions

Taken together, these data indicate that a deficiency of CX3CR1 is permissive to protracted microglial activation and prolonged behavioral alterations in response to transient activation of the innate immune system. http://www.jneuroinflammation.com/content/7/1/93---

Subject: RE: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "MB12 valtrex" <mb12valtrex >Date: Friday, January 11, 2013, 10:57 AM

Yes this could be the case - what does over-activated actually mean though - what part of their molecular structure is high

To: mb12valtrex From: sailcharters@...Date: Fri, 11 Jan 2013 04:57:19 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The microglia are overactivated. they also appear shriveled and damaged in post mortem brain tissue of children with autism meaning may cause abnormal signaling.

See photo of microglia here in a child with autism vs a typical child

http://sfari.org/news-and-opinion/in-brief/2010/molecular-mechanisms-autism-brains-show-activated-immune-defense?searchterm=angry+microglia%2C+autism

Scientists capture microglia's role in brain connectivity

E-mailPrint Share This

Popularity tracker

Virginia

20 December 2010

PLoS Biol.

Pruning partners: After mice are left for days in the dark (top), their microglia (black) are more likely to engulf parts of the synapse (pink) than are those of mice re-exposed to light (above).

Scientists are changing their minds about the role of microglia, the brain's strongest and most agile soldiers against damage and infection.

Microglia are versatile beyond the immune system, and could be important for neurological disorders, including autism, according to a study published 2 November in PLoS Biology1.

Using high-tech imaging, the researchers captured dynamic, ongoing interactions between microglia and synapses — the junctions between neurons — showing that, in healthy brains, microglia help build and eliminate synapses.

"Our work suggests that these cells are not just sitting around waiting for something horrible to happen to the brain. They're actually doing important things all the time to help with brain function, and synaptic function in particular," notes lead investigator Ania Majewska, assistant professor of neurobiology and anatomy at the University of Rochester in New York.

This influence on brain connectivity could explain why microglia keep popping up in studies of cognitive disorders ranging from Alzheimer's and Parkinson's diseases to Rett syndrome and autism. In 1990, Graeber, chair of brain tumor research at the University of Sydney in Australia, first proposed that microglia are the main component of the brain's 'immune network2.' At the time, most people thought that the cells are usually at rest, dramatically changing shape in the presence of an infection and engulfing foreign particles.

In 2005, however, a German team discovered that the term 'resting microglia' is an oxymoron: the cells' branches are in fact continually reaching out to their cellular neighbors — acting, as the researchers put it, like "busy and vigilant housekeepers3."

"Their little processes are zipping away all over the place," Majewska says. Her new study suggests that this activity is much more than an infection patrol.

Her team took close-up pictures and videos of microglia in the visual cortex of young mice. They chose this region partly because its activity can be probed simply by changing light conditions.

One method, called two-photon imaging, captures the interactions of cells in live mice. By genetically engineering the mice so that microglia glow yellow and neurons green, the researchers could watch the cells dancing together in real time.

Using electron microscopy — which gives a high-resolution picture of fixed tissue — the researchers found that microglia touch and wrap around several parts of the synapse. In animals that had been deprived of light for about a week, microglia are larger and have more of these interactions with the synaptic cleft, the tiny gap between two neurons.

What's more, in mice exposed to darkness, microglia are more likely to have engulfed parts of the synapse, suggesting that the cells are helping the brain adapt by pruning unnecessary connections.

"This paper is a breakthrough in that it really demonstrates that microglia respond to experience," Graeber says.

The findings align with a perspective he published 5 November in Science4, in which he proposed that, more than soldiers or housekeepers, microglia are like electricians: maintaining and installing electrical equipment from outside the circuit.

Autism activation:

Microglia have been a hot topic in the autism field since 2005, when a group led by Pardo identified activated microglia and inflammation in postmortem brain tissue from children with autism5.

In August, Pardo and colleagues looked at the structure of microglia in much more detail. They again found an abundance of activated microglia in autistic brains, and showed that the cells are larger and denser6.

Because of microglia's reputation as infection-fighters, these reports have fueled speculation that the immune system is disrupted in people with autism. But the new work shows that microglial shape-shifting happens all the time, and not necessarily as a marker of immune response.

Using a sophisticated imaging technique, researchers visualized the intricate interactions between neurons (green) and microglia (yellow).

"We still don't have a good explanation for why microglia are activated in autism," says Pardo, associate professor of neurology and pathology at s Hopkins University in Baltimore. "It could be because there is a protective factor, or it could be in response to synaptic abnormalities. We just don't know."

Clarifying the role of these cells in autism could lead to a new class of treatments. Because microglia operate independently of neurons, drugs might be targeted to microglia without affecting cell circuitry. "Microglia are more amenable to therapy than neurons," notes Lee-Way Jin, associate professor of pathology at the M.I.N.D. Institute at the University of California, .

For a study published earlier this year, Jin and collaborator Izumi Maezawa harvested microglia from healthy mice and those missing MeCP2, the gene that causes Rett syndrome. Looking in cultured cells, they found that in the presence of the mutant microglia, neurons grow with stunted dendrites, the long projections that receive electric signals7.

Jin is developing a drug that blocks a potassium channel that is specific to microglia. Targeting the channel might allow researchers to regulate the action of the microglia. "But we have to walk a fine line — we want to inhibit microglia activation, but also preserve its beneficial effects."

References:

Tremblay M.È. et al. PLoS Biol. 8, e1000527 (2010) PubMed

Graeber M.B. and W.J. Streit Brain Pathol. 1, 2-5 (1990) PubMed

> wrote:

Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "mb12valtrex " <mb12valtrex >Date: Friday, January 11, 2013, 6:45 AM

Yes the article says that it is confusing because they are also needed for a healthy brain. Maybe it makes a difference what causes the activation. If it is the immune system or if it is the healthy activity?

Sent from my iPhone

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

E-mailPrint Share This

Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,†notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.â€

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,†Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,†Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,†Kipnis says, “but it’s not meaningful enough.â€

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

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All super interesting . Thanks for sending all these links. RuthSent from my iPhone

These studies may shed some light..

Nat Neurosci. 2006 Jul;9(7):917-24. Epub 2006 Jun 18.

Control of microglial neurotoxicity by the fractalkine receptor.

Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S,

Lira SA, Littman DR, Ransohoff RM.

Source

Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland, Ohio 44195, USA.

Abstract

Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

http://www.ncbi.nlm.nih.gov/pubmed/16732273

Role of fractalkine (CX3CL1) in regulating neuron-microglia interactions: development of viral-based CX3CR1 antagonists.

Streit WJ, CN, on JK.

Source

Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA. streit@...

Abstract

Blocking the effects of fractalkine therapeutically may regulate microglia cell activation and provide neuroprotection in the AD brain. A human herpesvirus 8-encoded chemokine, termed vMIP-II is a non-selective chemokine receptor antagonist (binding multiple chemokine receptors, including CX3CR1). By comparing vMIP-II and FKN, we have generated molecules that selectively antagonize CX3CR1 activation. The results from these studies will guide future development of therapeutic agents designed to modulate microglial activation with the goal of preventing or slowing the progression of AD.

http://www.ncbi.nlm.nih.gov/pubmed/15974917

Fractalkine receptor (CX3CR1) deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide

W Corona1*, Yan Huang1, C O'Connor2,6, Dantzer2, W Kelley2, G Popovich3,4,5 and

P Godbout1,3,4,5*

* Corresponding authors: W Corona .Wynne@... - P Godbout .Godbout@...

Author Affiliations

1 Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA

2 Department of Animal Science, University of Illinois, 1201 W. Drive, 250B R. Madigan Laboratory, Urbana, IL 61820, USA

3 Institute for Behavioral Medicine Research, The Ohio State University, 460 Medical Center Dr., Columbus, OH 43210, USA

4 Center for Brain and Spinal Cord Repair, The Ohio State University, 460 W. 12th Ave, Columbus, OH 43210, USA

5 Department of Neuroscience, The Ohio State University, 333 W. 10th Ave, Columbus, OH 43210, USA

6 Department of Pharmacology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San , TX 78229, USA

For all author emails, please log on.

Journal of Neuroinflammation 2010, 7:93 doi:10.1186/1742-2094-7-93

The electronic version of this article is the complete one and can be found online at: http://www.jneuroinflammation.com/content/7/1/93

Received:

18 October 2010

Accepted:

17 December 2010

Published:

17 December 2010

© 2010 Corona et al.; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Interactions between fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) regulate microglial activation in the CNS. Recent findings indicate that age-associated impairments in CX3CL1 and CX3CR1 are directly associated with exaggerated microglial activation and an impaired recovery from sickness behavior after peripheral injection of lipopolysaccharide (LPS). Therefore, the purpose of this study was to determine the extent to which an acute LPS injection causes amplified and prolonged microglial activation and behavioral deficits in CX3CR1-deficient mice (CX3CR1-/-).

Methods

CX3CR1-/- mice or control heterozygote mice (CX3CR1+/-) were injected with LPS (0.5 mg/kg i.p.) or saline and behavior (i.e., sickness and depression-like behavior), microglial activation, and markers of tryptophan metabolism were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions.

Results

LPS injection caused a prolonged duration of social withdrawal in CX3CR1-/- mice compared to control mice. This extended social withdrawal was associated with enhanced mRNA expression of IL-1β, indolamine 2,3-dioxygenase (IDO) and kynurenine monooxygenase (KMO) in microglia 4 h after LPS. Moreover, elevated expression of IL-1β and CD14 was still detected in microglia of CX3CR1-/- mice 24 h after LPS. There was also increased turnover of tryptophan, serotonin, and dopamine in the brain 24 h after LPS, but these increases were independent of CX3CR1 expression. When submitted to the tail suspension test 48 and 72 h after LPS, an increased duration of immobility was evident only in CX3CR1-/- mice. This depression-like behavior in CX3CR1-/- mice was associated with a persistent activated microglial phenotype in the hippocampus and

prefrontal cortex. Conclusions

Taken together, these data indicate that a deficiency of CX3CR1 is permissive to protracted microglial activation and prolonged behavioral alterations in response to transient activation of the innate immune system. http://www.jneuroinflammation.com/content/7/1/93---

Subject: RE: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "MB12 valtrex" <mb12valtrex >Date: Friday, January 11, 2013, 10:57 AM

Yes this could be the case - what does over-activated actually mean though - what part of their molecular structure is high

To: mb12valtrex From: sailcharters@...Date: Fri, 11 Jan 2013 04:57:19 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The microglia are overactivated. they also appear shriveled and damaged in post mortem brain tissue of children with autism meaning may cause abnormal signaling.

See photo of microglia here in a child with autism vs a typical child

http://sfari.org/news-and-opinion/in-brief/2010/molecular-mechanisms-autism-brains-show-activated-immune-defense?searchterm=angry+microglia%2C+autism

Scientists capture microglia's role in brain connectivity

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Virginia

20 December 2010

PLoS Biol.

Pruning partners: After mice are left for days in the dark (top), their microglia (black) are more likely to engulf parts of the synapse (pink) than are those of mice re-exposed to light (above).

Scientists are changing their minds about the role of microglia, the brain's strongest and most agile soldiers against damage and infection.

Microglia are versatile beyond the immune system, and could be important for neurological disorders, including autism, according to a study published 2 November in PLoS Biology1.

Using high-tech imaging, the researchers captured dynamic, ongoing interactions between microglia and synapses — the junctions between neurons — showing that, in healthy brains, microglia help build and eliminate synapses.

"Our work suggests that these cells are not just sitting around waiting for something horrible to happen to the brain. They're actually doing important things all the time to help with brain function, and synaptic function in particular," notes lead investigator Ania Majewska, assistant professor of neurobiology and anatomy at the University of Rochester in New York.

This influence on brain connectivity could explain why microglia keep popping up in studies of cognitive disorders ranging from Alzheimer's and Parkinson's diseases to Rett syndrome and autism. In 1990, Graeber, chair of brain tumor research at the University of Sydney in Australia, first proposed that microglia are the main component of the brain's 'immune network2.' At the time, most people thought that the cells are usually at rest, dramatically changing shape in the presence of an infection and engulfing foreign particles.

In 2005, however, a German team discovered that the term 'resting microglia' is an oxymoron: the cells' branches are in fact continually reaching out to their cellular neighbors — acting, as the researchers put it, like "busy and vigilant housekeepers3."

"Their little processes are zipping away all over the place," Majewska says. Her new study suggests that this activity is much more than an infection patrol.

Her team took close-up pictures and videos of microglia in the visual cortex of young mice. They chose this region partly because its activity can be probed simply by changing light conditions.

One method, called two-photon imaging, captures the interactions of cells in live mice. By genetically engineering the mice so that microglia glow yellow and neurons green, the researchers could watch the cells dancing together in real time.

Using electron microscopy — which gives a high-resolution picture of fixed tissue — the researchers found that microglia touch and wrap around several parts of the synapse. In animals that had been deprived of light for about a week, microglia are larger and have more of these interactions with the synaptic cleft, the tiny gap between two neurons.

What's more, in mice exposed to darkness, microglia are more likely to have engulfed parts of the synapse, suggesting that the cells are helping the brain adapt by pruning unnecessary connections.

"This paper is a breakthrough in that it really demonstrates that microglia respond to experience," Graeber says.

The findings align with a perspective he published 5 November in Science4, in which he proposed that, more than soldiers or housekeepers, microglia are like electricians: maintaining and installing electrical equipment from outside the circuit.

Autism activation:

Microglia have been a hot topic in the autism field since 2005, when a group led by Pardo identified activated microglia and inflammation in postmortem brain tissue from children with autism5.

In August, Pardo and colleagues looked at the structure of microglia in much more detail. They again found an abundance of activated microglia in autistic brains, and showed that the cells are larger and denser6.

Because of microglia's reputation as infection-fighters, these reports have fueled speculation that the immune system is disrupted in people with autism. But the new work shows that microglial shape-shifting happens all the time, and not necessarily as a marker of immune response.

Using a sophisticated imaging technique, researchers visualized the intricate interactions between neurons (green) and microglia (yellow).

"We still don't have a good explanation for why microglia are activated in autism," says Pardo, associate professor of neurology and pathology at s Hopkins University in Baltimore. "It could be because there is a protective factor, or it could be in response to synaptic abnormalities. We just don't know."

Clarifying the role of these cells in autism could lead to a new class of treatments. Because microglia operate independently of neurons, drugs might be targeted to microglia without affecting cell circuitry. "Microglia are more amenable to therapy than neurons," notes Lee-Way Jin, associate professor of pathology at the M.I.N.D. Institute at the University of California, .

For a study published earlier this year, Jin and collaborator Izumi Maezawa harvested microglia from healthy mice and those missing MeCP2, the gene that causes Rett syndrome. Looking in cultured cells, they found that in the presence of the mutant microglia, neurons grow with stunted dendrites, the long projections that receive electric signals7.

Jin is developing a drug that blocks a potassium channel that is specific to microglia. Targeting the channel might allow researchers to regulate the action of the microglia. "But we have to walk a fine line — we want to inhibit microglia activation, but also preserve its beneficial effects."

References:

Tremblay M.È. et al. PLoS Biol. 8, e1000527 (2010) PubMed

Graeber M.B. and W.J. Streit Brain Pathol. 1, 2-5 (1990) PubMed

> wrote:

Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: "mb12valtrex " <mb12valtrex >Date: Friday, January 11, 2013, 6:45 AM

Yes the article says that it is confusing because they are also needed for a healthy brain. Maybe it makes a difference what causes the activation. If it is the immune system or if it is the healthy activity?

Sent from my iPhone

It is also very well known that people who study or spend a lot of time doing anything eg piano or an education subject or dance or conversation or anything else get much more activated glia. It is glia activation that correlates to learning. The brain is 85% glia, so to say the brain being activated is a problem is nonsense

To: mb12valtrex From: sailcharters@...Date: Thu, 10 Jan 2013 17:31:18 -0800Subject: Re: Autism Speaks now saying that there is more evidence of microglial activation in Autism

The news story below was posted today on the SFARI web site

Brain imaging study points to microglia as autism biomarker

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Popularity trackerVirginia

10 January 2013

Rainbow bright: The brain of an individual with autism (bottom) shows more activated microglia than a control brain does (top).

Microglia, brain cells that are part of the immune system, are more activated in young men with autism than in controls, according to a brain imaging study published 26 November in the Archives of General Psychiatry1.

Postmortem studies have shown that microglia are altered in autism, but the new study marks the first time that researchers have tracked the cells in living people with the disorder.

Microglia are known to rapidly transform from a spider-shaped resting state into a bulbous active state when they’re fighting off infection or damage. But the role of activated microglia in autism and related disorders is complex and largely mysterious. For example, studies in the past couple of years have shown that active microglia are important not only for immunity, but for the development of a healthy brain.

It’s not yet clear what the findings from the new study mean. But experts say that tracking microglia activity in live brains could be used as a biomarker of how the brain changes over time, such as before and after a new treatment.

“Doing this in vivo characterization gives a more dynamic perspective of what these cells are doing in the brain,†notes Pardo, associate professor of neurology and neuropathology at s Hopkins University in Baltimore, who was not involved in the work.

In the new study, researchers from Japan used a type of brain scanning called positron emission tomography (PET) to track the distribution of microglia in the brain. Their scans point to an abundance of activated microglia in men with autism, particularly in the cerebellum — a region known to process sensory information, movement and learning, and which has also been linked to autism.

The data echo what’s been seen in postmortem tissue. For example, in a landmark study in 2005, Pardo’s team showed that cerebellar tissue from individuals with autism shows an excess of activated microglia and contains certain chemicals, called cytokines, that are involved in inflammatory responses2.

Tricky tracer:

In PET scanning, radioactive tracers injected into participants’ blood make their way into the brain, bind to specific receptors, and can then be seen with a brain scanner.

In this case, the researchers used a tracer dubbed [11C]®-PK11195, which binds to activated microglia. The tracer has been used for decades in people with various neurological disorders. It had not been used in people with autism, however, because the link between microglia and the disorder is relatively new.

The researchers injected the tracer into 20 men with high-functioning autism and 20 controls matched by sex, age and intelligence quotient. They found that the tracer binds more strongly in the brains of the participants with autism, presumably because they have more activated microglia.

This was true across all brain regions tested, says lead investigator Kazuhiko Nakamura, associate professor of psychiatry and neurology at Hamamatsu University School of Medicine in Shizuoka, Japan. “But the most prominent increase was evident in the cerebellum.â€

No one knows what activated microglia may be doing in the brains of people with autism, some experts note. Others are concerned by some of the details of the study’s design.

For example, the tracer isn’t specific to activated microglia. It can also bind other brain cells, including astrocytes, star-shaped cells whose long projections help support synapses, the junctions between neurons.

Less frequently, the tracer also binds resting microglia and neurons, notes Innis, chief of the molecular imaging branch of the National Institute of Mental Health, who was not involved in the new study.

Innis is using tracers that are more specific to activated microglia in people with autism. Nakamura says his team, too, is developing more specific tracers.

The new study’s design is also not ideal, according to Innis, because the researchers didn’t simultaneously look at the tracer in both the blood and brain. This comparison can rule out the possibility that people with autism simply process the tracer differently.

“Maybe the patients are just not metabolizing this drug as fast, and therefore more of it is getting into the brain,†Innis says.

Nakamura agrees that this is a possibility, but argues that metabolic abnormalities are unlikely because the scans indicated that there were no differences in blood flow in the brains of people with autism and controls.

Because it requires exposure to radiation, PET scanning is usually not done on children, especially for studies that require a healthy control group.

But newer microglia markers that require less radiation than conventional markers could conceivably be used to track the effectiveness of a therapy. “I could see it being extended into research studies of anti-inflammatory therapies, where the child acts as their own control,†Innis says.

Methodological issues aside, other researchers question the meaning of the data. Several big questions remain unanswered, such as whether activated microglia are a cause or consequence of autism, notes Kipnis, professor of neuroscience at the University of Virginia in Charlottesville.

Last year, Kipnis’ team reported that replacing the microglia in mice that model Rett syndrome alleviates some symptoms and extends the mice’s lives. Intriguingly, these mutant animals seem to have under-active microglia, he says, illustrating that the cells’ role in neurodevelopmental disorders is not straightforward.

“Just looking at the number of microglia, and whether they’re activated or not — I’m not saying it’s meaningless,†Kipnis says, “but it’s not meaningful enough.â€

References:

1: Suzuki K. et al. JAMA Psychiatry Epub ahead of print (2012) Abstract

SOURCE:http://sfari.org/news-and-opinion/news/2013/brain-imaging-study-points-to-microglia-as-autism-biomarker---

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol

[Guest guest]

you're welcome.. now lets hope they can come up with an effective treatment to regulate the overactive microglia in our kids!

Subject: Autism Speaks now saying that there is more evidence of microglial activation in AutismTo: stopcallingitautism , stopcallingitautismfordoctors , mb12valtrex , GFCFKids Date: Tuesday, January 8, 2013, 10:49 PM

Go figure... That Autism Speaks denied us several requests for a grant for a treatment that we have used to treat microglial activation that cured my own son from autism and is helping many others. But now they are saying that there is more evidence of microglial activation in autism. Do they really want to find a cure for autism? http://www.sciencedaily.com/releases/2012/11/121126164308.htm

Thanks, Founder and Director of Stop Calling It Autism!http://www.stopcallingitautism.orgFax: or (888) SCIA-123

SCIA For Doctors Yahoo! Grouphttp://www.stopcallingitautism.org/fordoctors.html

SCIA Yahoo! Group (English)http://health.groups.yahoo.com/group/stopcallingitautism

SCIA Facebook Group (English)http://www.facebook.com/groups/stopcallingitautism

SCIA Yahoo! Group (Spanish)http://health.groups.yahoo.com/group/stopcallingitautismespanol

SCIA Facebook Group (Spanish)http://www.facebook.com/groups/stopcallingitautismespanol