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As I said, oxytosis, otherwise known as excitotoxicity or glutamate toxicity
In the last couple of days, I have been posting on the sulfur deficiency thread and elsewhere on this site about my work "Hypothesis: Chronic Fatigue Syndrome, Mitochondrial Hypo-function, and Hydrogen Sulfide"
In part, I said:
"A further known complication for some people is a CBS polymorphism. The body produces hydrogen sulfide through several enzymes, including cystathionine beta synthase (CBS). CBS produces H2S in the brain, where it modulates NMDA glutamate receptor function. H2S protects neurons from glutamate toxicity by increasing the production of glutathione. Long-term potentiation is altered in the absence of H2S, which suggests the involvement of H2S in synaptic activity, so looking more closely at CBS and H2S is very important."
...and earlier today I wrote another post on the same thread:
"As for the neurons, we know that "H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of ?- glutamylcysteine synthetase and up-regulating cystine transport. Cystine (cysteine) is the rate- limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione"." I then mentioned that I believe cysteine and NAC to be as important as B-12.
Oxytosis, of course, is "excitoxicity" or glutamate toxicity, which results in nerve cell death.
While your comments parallel mine (without any reference to them), I note that you didn't include the part about the role of H2S increasing the production of glutathione or protecting the neurons from glutamate toxicity. I believe this is critical for a full understanding of what is happening in the brains of people with ME/CFS. I am wondering, were you aware of the potential problem with glutamate toxicity prior to my postings? Have you written about this problem anywhere before, including the role that H2S plays? I think that glutamate toxicity is important for people to be aware of, particularly those with the CBS SNP.
The astrocyte connection to the mitochondria is intriguing as I believe that ME/CFS is a mitochondrial disease and that hydrogen sulfide plays a critical role in the mitochondria as well. From what I have read, "the results seem to indicate that astrocytes provide neurons mainly with CSH (cysteine), rather than GSH (glutathione), as the antioxidant material for neuroprotection." (PMID: 21436138) Do you have the citation for what you have described? As always, I appreciate your time.
Marian
Hi Rich,Hi, justy.
I think that what you are experiencing are symptoms of excitotoxicity. This means that there is too much glutamate remaining in the synapses of your neurons, and it is overexciting the NMDA receptors. Normally, the excess glutamate is pumped out of the synapses by the astrocytes, which are "helper" cells also in the brain. The astrocytes normally convert the glutamate to glutamine and give it back to the neurons so they can use it again to make glutamate as needed. Both the pumping and the conversion require ATP, which is mostly made by the mitochondria in the astrocytes.
If the astrocytes go low in glutathione, which occurs in ME/CFS, then the mitochondria become dysfunctional and are not able to produce ATP at as high a rate as normal. This causes an "energy crisis" both for the pumps and for the glutamine sythetase reaction. The result is that too much glutamate stays in the synapses, and the person experiences the symptoms of excitotoxity (anxiety, insomnia, a "wired" feeling or "nervousness").
Rich
In the last couple of days, I have been posting on the sulfur deficiency thread and elsewhere on this site about my work "Hypothesis: Chronic Fatigue Syndrome, Mitochondrial Hypo-function, and Hydrogen Sulfide"
In part, I said:
"A further known complication for some people is a CBS polymorphism. The body produces hydrogen sulfide through several enzymes, including cystathionine beta synthase (CBS). CBS produces H2S in the brain, where it modulates NMDA glutamate receptor function. H2S protects neurons from glutamate toxicity by increasing the production of glutathione. Long-term potentiation is altered in the absence of H2S, which suggests the involvement of H2S in synaptic activity, so looking more closely at CBS and H2S is very important."
...and earlier today I wrote another post on the same thread:
"As for the neurons, we know that "H2S increases the glutathione levels, which normally decrease during the cell death cascade, by enhancing the activity of ?- glutamylcysteine synthetase and up-regulating cystine transport. Cystine (cysteine) is the rate- limiting substrate of glutathione synthesis. These observations reveal that H2S protects neurons from oxytosis by increasing the production of the antioxidant glutathione"." I then mentioned that I believe cysteine and NAC to be as important as B-12.
Oxytosis, of course, is "excitoxicity" or glutamate toxicity, which results in nerve cell death.
While your comments parallel mine (without any reference to them), I note that you didn't include the part about the role of H2S increasing the production of glutathione or protecting the neurons from glutamate toxicity. I believe this is critical for a full understanding of what is happening in the brains of people with ME/CFS. I am wondering, were you aware of the potential problem with glutamate toxicity prior to my postings? Have you written about this problem anywhere before, including the role that H2S plays? I think that glutamate toxicity is important for people to be aware of, particularly those with the CBS SNP.
The astrocyte connection to the mitochondria is intriguing as I believe that ME/CFS is a mitochondrial disease and that hydrogen sulfide plays a critical role in the mitochondria as well. From what I have read, "the results seem to indicate that astrocytes provide neurons mainly with CSH (cysteine), rather than GSH (glutathione), as the antioxidant material for neuroprotection." (PMID: 21436138) Do you have the citation for what you have described? As always, I appreciate your time.
Marian