CAN item on neuroimmune research

[Guest guest]

the interesting thing - a few of us have contacted folks at JHU

regarding Neuroimmune dysfunction and Autism. and we've been told

either 'no such thing in Autism' or 'it hasn't been proven. Nice

idea though...' perhaps it was because we didn't offer them any

money ....

doris

-maryland

Neuroimmune Researchers Funded by Cure Autism Now Chosen to Give

Public Forum Lecture on Autism

Autism reaches the mainstream of basic science research in neurochemistry

The American Society for Neurochemistry (ASN) addressed autism this year

at its annual conference, which was held this June in Madison,

Wisconsin. Two Cure Autism Now funded researchers, Dr. Pardo of

's Hopkins University and Dr. Boulanger of the University of

California, San Diego, were invited to be keynote speakers in the ASN's

public forum, a segment of the annual conference offered to raise public

awareness about ongoing research in the field of neuroscience. Dr. Pardo

and Dr. Boulanger spoke about their research involving immune mechanisms

in autism to an audience mostly comprised of parents of children living

with the disorder.

Dr. Pardo's presentation focused on his research that examines the role

of neuroinflammation in the pathogenesis of autism. Studies in his

laboratory involve use of post-mortem human brain tissue that compared

the differences between brain tissue from autistic individuals and brain

tissue from normal controls on a cellular level. Dr. Pardo and

colleagues found that two important cell types, microglia and astroglia,

were activated in the autistic brain tissue. Both microglia and

astroglia, which are only found in the brain, serve as support cells for

neurons and also mediate immune responses in the central nervous system.

When activated these cells secrete chemicals called cytokines that can

either stimulate or inhibit further inflammation.

Dr. Pardo also spoke about another facet of his research involving the

examination of cerebral spinal fluid (CSF) of living patients. When

comparing the CSF of autistic individuals to CSF from normal controls

Dr. Pardo found that autistic people had higher levels of

pro-inflammatory cytokines (cytokines that stimulate inflammation) than

normal controls. Interestingly, pro-inflammatory cytokines were detected

at higher levels in autistic individuals regardless of age, a finding

that Dr. Pardo suggests may indicate that the inflammatory process in

autism continues into adulthood. Although these are extremely important

observations, Dr. Pardo also explained that the role of

neuroinflammation in autism is not yet understood. For instance, it is

not known whether the inflammation observed in the brain and CSF of

autistic patients actually participates in causing autism, or whether it

is a compensatory reaction to having autism. Dr. Pardo also cautioned

that we don't know whether the neuroinflammation is a protective

response or a harmful mechanism that further promotes the symptoms of

autism. For these reasons, understanding the role of inflammation in

autism remains a research priority. Dr. Pardo and colleagues are

currently designing additional studies characterizing the CSF from

autistic individuals to more specifically address the role that

neuroinflammation plays in the development of autism. Finding people to

participate in the studies will be crucial to their success. Individuals

interested can contact Dr. Pardo directly at cpardo@...

<mailto:cpardo@...>.

Dr. Pardo's CAN-funded studies on neuroinflammation have also attracted

the attention of the environmental science community. Dr. Pardo has been

invited to speak about neuroinflammation and the pathogenesis of autism

at a National Institute of Environmental Health Sciences (NIEHS)

conference in September that will focus on the environment and

neurodevelopmental disorders, including autism. The NIEHS is the branch

of the National Institutes of Health devoted to environmental health and

environment-related diseases. More information about this conference can

be found at http://www.neurotoxicology.com/conference.htm

Dr. Boulanger's research also examines the role of the immune system in

autism. At the public forum, Dr. Boulanger presented her work on how

changes of a specific protein of the immune system, called MHC-I, can

affect brain development and function. Dr. Boulanger actually started

her career in neuroscience studying how brain circuitry is formed, and

became interested in the role of immune signaling in the normal

development of the brain. She began working on autism after learning of

recent studies that linked autism to alterations in genes of the immune

system and immune responses. Dr. Boulanger now hypothesizes that since

MHC-I likely has a role in brain development and function, it may be

altered in autism.

In her laboratory, Dr. Boulanger uses genetically altered mice that are

deficient in MHC-I expression to address this important research

question. Until recently, MHC-I proteins were not even thought to exist

in neurons. Dr. Boulanger and colleagues have since demonstrated that

normal, healthy neurons do make MHC-I. Interestingly, areas of the brain

that are undergoing a late developmental step involving the formation of

precise neuronal connections (a process that requires the removal of

inappropriate connections) contain particularly high levels of MHC-I.

Even though brain remodeling occurs throughout your lifetime, the peak

period of sculpting neuronal connections is during early postnatal life.

This is the time in which children with autism have been found to have

increased brain sizes. Therefore, given what is known about brain

overgrowth in autism, Dr. Boulanger and others have postulated that

unusual strategies for locomotion, oversensitivity to light, sounds and

smells may result from a failure to remove inappropriate neuronal

connections which occurs during the normal development of the brain.

By using the eye as a model system and an innovative technology that

allows tracking of individual neurons from the eye as they reach targets

in the brain, Dr. Boulanger found visual inputs in mice without MHC-I

make imprecise connections. These data suggest a critical role for MHC-I

in the early development of the visual system and possibly other parts

of the brain that use similar mechanisms to achieve perfect wiring. With

her CAN grant, Dr. Boulanger is now focusing on the exact role of MHC-I

in the remodeling process, and on what factors can influence the

expression and function of MHC-I in the developing brain, hoping that

this will provide guidance as to what processes may be affected in

autism. Dr. Boulanger is also currently examining a mouse model

developed by Dr. at the California Institute of

Technology (Caltech). When these mice are exposed to immune challenges

during the fetal and postnatal period the mice go on to develop

macrocephaly (large brains) and other brain structure abnormalities

reminiscent of those seen in autism. Dr. Boulanger hopes that all of

this work will shed light on the crucial and not-well understood link

between immune system activation and brain circuit formation, an

interaction that may be important to the development of autism.

Although the clinical link between Dr. Pardo's and Dr. Boulanger's work

is evolving, it is believed that the expression of MHC-I in the brain is

regulated by cytokines. Both researchers hypothesize that immune

challenges that occur early in fetal and postnatal period can affect

cytokine expression and may lead to abnormal brain development. Dr.

Pardo's results suggest that there is a role for cytokines and

inflammation in the pathogenesis of autism. Dr. Boulanger's results

raise the possibility that immune challenges (such as a viral infection)

may also be changing levels of MHC-I proteins in the brain, potentially

offering an important link between immune system activation and brain

wiring. They both caution, however, that the link between autism and

inflammation is preliminary and may only be relevant in a subset of

patients. Finally, although this work will hopefully have implications

for treatment strategies, they both note that many current medications

we know as being " anti-inflammatory " for the body may not also affect

inflammation in the brain.

The excellent work of these two CAN-funded researchers suggests a strong

role for the immune system in the pathogenesis of autism. Their research

presents exciting new opportunities for additional studies that will

investigate the role of inflammation, cytokines, and immune proteins

such as MHC-I in the development of this disorder. A critical result of

these CAN funded studies is that both Dr. Boulanger and Dr. Pardo are

currently collaborating with many other research scientists in the

immune community. Their work has stimulated a growing interest in the

scientific community about how the neuroimmune system is involved in

autism, thereby pushing the study of autism further into the mainstream

of basic science research. Dr. Pardo enthusiastically thanked Cure

Autism Now, stating that " we were having difficulty finding funding for

our novel ideas - it wasn't until Cure Autism Now supported our research

that we were able to explore the link between neuroinflammation and autism. "

Cure Autism Now congratulates Dr. Pardo and Dr. Boulanger on their work

and for being chosen to speak in such an important public forum.