Dunmann, thanks for posting this. I think it could be important information. If I understood the article correctly (no guarantee there btw), this is confirmation that glutamate receptors may be involved in the loss of myelin in MS. I think Dignan posted something about glutamate excitoxicity a while back. Here’s some more info:
Simultaneous Neuroprotection and Blockade of Inflammation Reverses Auto Immune Encephalitis
Myelin, oligodendrocytes and neurons are lost due to the release by immune cells of cytotoxic cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter glutamate.
(Bromley that first abstract is authored by some of your favorite researchers in New Zealand.)Glutamate Inhibition in MS: the Neuroprotective Properties of Riluzole
Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial.Excitatory Amino Acids: Evidence from CSF
CONCLUSIONS: Neurotoxic events occur in MS patients, and they can be responsible for oligodendrocyte and neuronal cell death in patients with this demyelinating disease. The manipulation of glutamate-altered homeostasis or antagonizing glutamate receptor-mediated excitotoxicity may have therapeutic implications in MS patients.
If you’re wondering why I’ve checked this out it’s because, sigh, of course, hormones ease glutamate excitotoxicity. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons
We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid beta-peptide (A beta) toxicity. The toxicity of each insult was significantly attenuated in cultures pretreated for 2 h with 100 nM-10 microM 17 beta-estradiol, estriol, or progesterone.
corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and A beta.
We conclude that estrogens, progesterone, and corticosterone can directly affect neuronal vulnerability to excitotoxic, metabolic, and oxidative insults, suggesting roles for these steroids in several different neurodegenerative disorders.
Guys, you have progesterone too. Progesterone: the forgotten hormone in men?
Other progesterone effects in men include those on the central nervous system (CNS) (mainly mediated by 5alpha-reduced progesterone metabolites as so-called neurosteroids)The Case for Progesterone
estrogens have been given the primary focus despite the fact that progesterone has important properties that can enhance the repair of neurodegenerative and traumatic injuries to the central nervous system.
progesterone should be given more attention as a potent neurotrophic agent that may play an important role in reducing or preventing motor, cognitive, and sensory impairments that can accompany senescence in both males and females.
IMO it should be given more attention as a potent neurotrophic agent for reducing or preventing motor, cognitive, and sensory impairments than can accompany MS, not just senescence.
I've got that too.
Maybe this finding about glutamate and myelin will spur it along. I’m hoping. Progesterone is in a Phase III Clinical Trial for TBI.
The article mentions a drug already on the market that blocked the glutamate pores on the myelin sheath. Does anyone know what that drug is?
GWA—I am equally skeptical of EAE rodent studies, but they’re what we have at this point unfortunately.