Re: Melatonin-mitochondria Interplay in Health and Disease.

May 15, 2012

Hi Darla

Can't provide you with free access but if you find them on PubMed (this is the

link for one -http://www.ncbi.nlm.nih.gov/pubmed/21244359) you can link to the

full text via the publisher in top right hand corner and they'll tell you how to

pay for access.

HTH

Patience

>

> I am trying to puzzle together some of the mystery that is my son's

> dependence on melatonin - which has always worried me - he simply is unable

> to function without it. And I don't mean just sleep, I mean that he is

> dependent on it for a vastly improved quality of life. This is deeply

> puzzling to me as I have yet to encounter any other ASD child with a

> similar response. He presents with some symptoms that a paed neurologist

> speculated could be metabolic or mitochondrial in orgin (a neuromuscular

> issue) and I wonder if there is some correlation between the oxidative

> stress / nitrosative stress aspects of melatonin and his possible meta/mito

> issues. I would really like to read these full articles - is there anyone

> who might have access who would kindly be able to access it for me? Or

> does anyone know how I might pay to access them? (these are pubmed searches)

> Melatonin-mitochondria Interplay in Health and Disease.

>

> Castroviejo

DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%5D>

> , LÃ³pez

LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5D>

> , Escames

G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> , LÃ³pez

A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D>

> , GarcÃa

JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%5D>

> , Reiter

RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>

> .

>

> Centro de InvestigaciÃ³n BiomÃ©dica, Parque TecnolÃ³gico de Ciencias de la

> Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.

>

dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFt\

BBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ>

> .

> Abstract

>

> Although two main hypotheses of mitochondrial origin have been proposed,

> i.e., the autogenous and the endosymbiotic, only the second is being

> seriously considered currently. The 'hydrogen hypothesis' invokes metabolic

> symbiosis as the driving force for a symbiotic association between an

> anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the

> symbiont) that was able to respire, but which generated molecular hydrogen

> as an end product of anaerobic metabolism. The resulting proto-eukaryotic

> cell would have acquired the essentials of eukaryotic energy metabolism,

> evolving not only aerobic respiration, but also the physiological cost of

> the oxygen consumption, i.e., generation of reactive oxygen species (ROS)

> and the associated oxidative damage. This is not the only price to pay for

> respiring oxygen: mitochondria possess nitric oxide (NOÂ·) for regulatory

> purposes but, in some instances it may react with superoxide anion radical

> to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite

> anion, and the subsequent nitrosative damage. New mitochondria contain

> their own genome with a modified genetic code that is highly conserved

> among mammals. The transcription of certain mitochondrial genes may depend

> on the redox potential of the mitochondrial membrane. Mitochondria are

> related to the life and death of cells. They are involved in energy

> production and conservation, having an uncoupling mechanism to produce heat

> instead of ATP, but they are also involved in programmed cell death.

> Increasing evidence suggest the participation of mitochondria in

> neurodegenerative and neuromuscular diseases involving alterations in both

> nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful

> antioxidant and anti-inflammatory and increasing experimental and clinical

> evidence shows its beneficial effects against oxidative/nitrosative stress

> status, including that involving mitochondrial dysfunction. This review

> summarizes the data and mechanisms of action of melatonin in relation to

> mitochondrial pathologies.

>

> *Melatonin role in the mitochondrial function.*

> Acuna-Castroviejo

>

D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAuthor%5\

D>

> , Escames

G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>

> ,

MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D>

> ,

LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>

> .

> S

>

> Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de

> Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...

> Abstract

>

> Melatonin is an ancient molecule

> present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in

> unicellular organisms at the very early moment of life. Initially

> identified as a secretory product of the pineal gland in mammals and in

> other species, it was considered a hormone related to reproduction. The

> evidence that melatonin is produced in many organs and tissues of the body,

> reaching concentrations higher than in the blood, support the multiplicity

> of the melatonin actions. The best-known actions of melatonin, currently

> supported by experimental and clinical data, include antioxidant and

> anti-inflammatory abilities, some of them involving genomic regulation of a

> series of enzymes. Besides, melatonin displays anticonvulsant and

> antiexcitotoxic properties. Most of the beneficial consequences resulting

> from melatonin administration may depend on its effects on mitochondrial

> physiology. The physiological effects of melatonin on normal mitochondria,

> its role to prevent mitochondrial impairment, energy failure, and apoptosis

> in oxidatively-damaged mitochondria, and the beneficial effects of the

> administration of melatonin in experimental and clinical diseases involving

> mitochondrial dysfunction and cell death, are revised.

>

May 15, 2012

I think Tom is too (and me) we also do well on 5htp to some extent but

are both doing fabulously on L-tryptophan.

Could it be that he is using it all up somewhere earlier down the chain

so is unable to make 5htp, serotonin as well. Could be some blockage

somewhere or could be a virus eating it all up.

Just guesses of course.

May 15, 2012

If there is a virus/inflammation it would be 'eating up' tryptophan, not

5-htp (that is why I am wary of tryptophan, as it can literally be

potential 'food' for pathogens).

That is, according to current knowledge - there are probably many

unknowns here...

>

> I think Tom is too (and me) we also do well on 5htp to some extent but

> are both doing fabulously on L-tryptophan.

> Could it be that he is using it all up somewhere earlier down the

chain

> so is unable to make 5htp, serotonin as well. Could be some blockage

> somewhere or could be a virus eating it all up.

> Just guesses of course.

>

May 15, 2012

These are very interesting Darla (unfortunately not available through my uni subscription). Melatonin also has relatively strong antiinflammatory effects, so could be that... If you stop supplementing it how soon do you see deterioration of symptoms - is it almost immediate or takes weeks or months to notice?

Another possibility is that melatonin affects his quality of sleep in such a way that it affects everything else - I believe 'dysfunctional' sleep (with unregulated cycles etc, so called circadian disorder) can have deep effects on neurotransmitters and hormones during waking hours.

BTW Have you seen this http://www.medpagetoday.com/PrimaryCare/SleepDisorders/3574

Now digressing but we saw this REM behaviour disorder (sitting up, punching and pulling hair in sleep) when first starting LDN years ago. Many report the same thing... No idea what it means and whether linked to melatonin etc but very intriguing. http://en.wikipedia.org/wiki/Rapid_eye_movement_behavior_disorderv

>> I am trying to puzzle together some of the mystery that is my son's> dependence on melatonin - which has always worried me - he simply is unable> to function without it. And I don't mean just sleep, I mean that he is> dependent on it for a vastly improved quality of life. This is deeply> puzzling to me as I have yet to encounter any other ASD child with a> similar response. He presents with some symptoms that a paed neurologist> speculated could be metabolic or mitochondrial in orgin (a neuromuscular> issue) and I wonder if there is some correlation between the oxidative> stress / nitrosative stress aspects of melatonin and his possible meta/mito> issues. I would really like to read these full articles - is there anyone> who might have access who would kindly be able to access it for me? Or> does anyone know how I might pay to access them? (these are pubmed searches)> Melatonin-mitochondria Interplay in Health and Disease.> > Castroviejo DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuthor%5D>> , LÃ³pez LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> , LÃ³pez A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%5D>> , GarcÃa JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuthor%5D>> , Reiter RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D>> .> > Centro de InvestigaciÃ³n BiomÃ©dica, Parque TecnolÃ³gico de Ciencias de la> Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.> dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postID=MC_sFtBBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ>> .> Abstract> > Although two main hypotheses of mitochondrial origin have been proposed,> i.e., the autogenous and the endosymbiotic, only the second is being> seriously considered currently. The 'hydrogen hypothesis' invokes metabolic> symbiosis as the driving force for a symbiotic association between an> anaerobic, strictly hydrogen-dependent (the host) and an eubacterium (the> symbiont) that was able to respire, but which generated molecular hydrogen> as an end product of anaerobic metabolism. The resulting proto-eukaryotic> cell would have acquired the essentials of eukaryotic energy metabolism,> evolving not only aerobic respiration, but also the physiological cost of> the oxygen consumption, i.e., generation of reactive oxygen species (ROS)> and the associated oxidative damage. This is not the only price to pay for> respiring oxygen: mitochondria possess nitric oxide (NOÂ·) for regulatory> purposes but, in some instances it may react with superoxide anion radical> to produce the toxic reactive nitrogen species (RNS), i.e. peroxynitrite> anion, and the subsequent nitrosative damage. New mitochondria contain> their own genome with a modified genetic code that is highly conserved> among mammals. The transcription of certain mitochondrial genes may depend> on the redox potential of the mitochondrial membrane. Mitochondria are> related to the life and death of cells. They are involved in energy> production and conservation, having an uncoupling mechanism to produce heat> instead of ATP, but they are also involved in programmed cell death.> Increasing evidence suggest the participation of mitochondria in> neurodegenerative and neuromuscular diseases involving alterations in both> nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known powerful> antioxidant and anti-inflammatory and increasing experimental and clinical> evidence shows its beneficial effects against oxidative/nitrosative stress> status, including that involving mitochondrial dysfunction. This review> summarizes the data and mechanisms of action of melatonin in relation to> mitochondrial pathologies.> > *Melatonin role in the mitochondrial function.*> Acuna-Castroviejo> D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5BAuthor%5D>> , Escames G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> , MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor%5D>> , LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>> .> S> > Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de> Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@...> Abstract> > Melatonin is an ancient molecule> present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in> unicellular organisms at the very early moment of life. Initially> identified as a secretory product of the pineal gland in mammals and in> other species, it was considered a hormone related to reproduction. The> evidence that melatonin is produced in many organs and tissues of the body,> reaching concentrations higher than in the blood, support the multiplicity> of the melatonin actions. The best-known actions of melatonin, currently> supported by experimental and clinical data, include antioxidant and> anti-inflammatory abilities, some of them involving genomic regulation of a> series of enzymes. Besides, melatonin displays anticonvulsant and> antiexcitotoxic properties. Most of the beneficial consequences resulting> from melatonin administration may depend on its effects on mitochondrial> physiology. The physiological effects of melatonin on normal mitochondria,> its role to prevent mitochondrial impairment, energy failure, and apoptosis> in oxidatively-damaged mitochondria, and the beneficial effects of the> administration of melatonin in experimental and clinical diseases involving> mitochondrial dysfunction and cell death, are revised.>

May 15, 2012

PS have a look at these (I have the first one in full version but cannot attach it now, remind me later)

http://www.ncbi.nlm.nih.gov/pubmed/22575905

http://www.ncbi.nlm.nih.gov/pubmed/22074583

Natasa x

> >> > I am trying to puzzle together some of the mystery that is my son's> > dependence on melatonin - which has always worried me - he simply is> unable> > to function without it. And I don't mean just sleep, I mean that he is> > dependent on it for a vastly improved quality of life. This is deeply> > puzzling to me as I have yet to encounter any other ASD child with a> > similar response. He presents with some symptoms that a paed> neurologist> > speculated could be metabolic or mitochondrial in orgin (a> neuromuscular> > issue) and I wonder if there is some correlation between the oxidative> > stress / nitrosative stress aspects of melatonin and his possible> meta/mito> > issues. I would really like to read these full articles - is there> anyone> > who might have access who would kindly be able to access it for me? Or> > does anyone know how I might pay to access them? (these are pubmed> searches)> > Melatonin-mitochondria Interplay in Health and Disease.> >> > Castroviejo> DA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Castroviejo%20DA%22%5BAuth\> or%5D>> > , LÃ³pez> LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20LC%22%5BAutho\> r%5D>> > , Escames> G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> > , LÃ³pez> A<http://www.ncbi.nlm.nih.gov/pubmed?term=%22L%C3%B3pez%20A%22%5BAuthor%\> 5D>> > , GarcÃa> JA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Garc%C3%ADa%20JA%22%5BAuth\> or%5D>> > , Reiter> RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reiter%20RJ%22%5BAuthor%5D\> >> > .> >> > Centro de InvestigaciÃ³n BiomÃ©dica, Parque TecnolÃ³gico de> Ciencias de la> > Salud, Avenida del Conocimiento s/n, 18100 Armilla, Granada, Spain.> >> dacuna@<http://health.groups.yahoo.com/group/Meta-mito-autism/post?postI\> D=MC_sFtBBeuHELrGyPHtXDxW8cx32GZSoLzABdcGlo-V6g05pi_NObaAGRlZVbmhrs5vKlQ\> >> > .> > Abstract> >> > Although two main hypotheses of mitochondrial origin have been> proposed,> > i.e., the autogenous and the endosymbiotic, only the second is being> > seriously considered currently. The 'hydrogen hypothesis' invokes> metabolic> > symbiosis as the driving force for a symbiotic association between an> > anaerobic, strictly hydrogen-dependent (the host) and an eubacterium> (the> > symbiont) that was able to respire, but which generated molecular> hydrogen> > as an end product of anaerobic metabolism. The resulting> proto-eukaryotic> > cell would have acquired the essentials of eukaryotic energy> metabolism,> > evolving not only aerobic respiration, but also the physiological cost> of> > the oxygen consumption, i.e., generation of reactive oxygen species> (ROS)> > and the associated oxidative damage. This is not the only price to pay> for> > respiring oxygen: mitochondria possess nitric oxide (NOÂ·) for> regulatory> > purposes but, in some instances it may react with superoxide anion> radical> > to produce the toxic reactive nitrogen species (RNS), i.e.> peroxynitrite> > anion, and the subsequent nitrosative damage. New mitochondria contain> > their own genome with a modified genetic code that is highly conserved> > among mammals. The transcription of certain mitochondrial genes may> depend> > on the redox potential of the mitochondrial membrane. Mitochondria are> > related to the life and death of cells. They are involved in energy> > production and conservation, having an uncoupling mechanism to produce> heat> > instead of ATP, but they are also involved in programmed cell death.> > Increasing evidence suggest the participation of mitochondria in> > neurodegenerative and neuromuscular diseases involving alterations in> both> > nuclear (nDNA) and mitochondrial (mtDNA) DNA. Melatonin is a known> powerful> > antioxidant and anti-inflammatory and increasing experimental and> clinical> > evidence shows its beneficial effects against oxidative/nitrosative> stress> > status, including that involving mitochondrial dysfunction. This> review> > summarizes the data and mechanisms of action of melatonin in relation> to> > mitochondrial pathologies.> >> > *Melatonin role in the mitochondrial function.*> > Acuna-Castroviejo> >> D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Acuna-Castroviejo%20D%22%5B\> Author%5D>> > , Escames> G<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Escames%20G%22%5BAuthor%5D>> > , > MI<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20MI%22%5BAuthor\> %5D>> > , > LC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22%20LC%22%5BAuthor%5D>> > .> > S> >> > Departamento de Fisiologia, Instituto de Biotecnologia, Universidad de> > Granada, Avenida de Madrid 11, E-18012 Granada, Spain. dacuna@> > Abstract> >> > Melatonin is an ancient molecule> > present<http://www.ncbi.nlm.nih.gov/pubmed/17127351#> in> > unicellular organisms at the very early moment of life. Initially> > identified as a secretory product of the pineal gland in mammals and> in> > other species, it was considered a hormone related to reproduction.> The> > evidence that melatonin is produced in many organs and tissues of the> body,> > reaching concentrations higher than in the blood, support the> multiplicity> > of the melatonin actions. The best-known actions of melatonin,> currently> > supported by experimental and clinical data, include antioxidant and> > anti-inflammatory abilities, some of them involving genomic regulation> of a> > series of enzymes. Besides, melatonin displays anticonvulsant and> > antiexcitotoxic properties. Most of the beneficial consequences> resulting> > from melatonin administration may depend on its effects on> mitochondrial> > physiology. The physiological effects of melatonin on normal> mitochondria,> > its role to prevent mitochondrial impairment, energy failure, and> apoptosis> > in oxidatively-damaged mitochondria, and the beneficial effects of the> > administration of melatonin in experimental and clinical diseases> involving> > mitochondrial dysfunction and cell death, are revised.> >>

May 15, 2012

Darla,

pdf of the second one here:

http://www.bioscience.org/u37153137/gaDTRQo7632rgysaGWQYT64356/2007/v12/af/2116/\

2116.pdf