Welcome to ThisIsMS also Viper.
All--I know it seems like an interruption to the discussion and I apologize for that but I wanted to respond to Jaded’s earlier inquiry.
Jaded—I don’t think there’s any easy way to tie all of this together. Researchers interested in HPA hyperactivity (hypersecretion of cortisol I think) and MS have started to try and tie some things together from that tiny corner of MS world of research. So, with regard to the stress hormone “cortisol” and/or glucocorticoids, here are a couple of abstracts about that.
The Role of Stress Response Systems for the Pathogenesis and Progression of MS
Insensitivity to glucocorticoid and beta-adrenergic modulation might be involved in overshooting inflammation in MS, whereas hyperactivity of the HPA axis has been linked to neurodegeneration and increased disability.
As nearly as I’ve been able to understand (since I understand very little in fact is why I feel compelled to provide links to abstracts many times) is that HPA hyperactivity translates to hypersecretion of the stress hormone cortisol.HPA Axis Activity Predicts Disease Progression in MS
In this longitudinal study over a 3-year follow-up period, we report that patients who exhibited stronger HPA reactivity at baseline were significantly more likely to experience progression as measured by the Expanded Disability Status Scale (EDSS) during the follow-up period. Furthermore, HPA axis activity correlated with progression ratings and cognitive impairment three years later. Tests of HPA axis activity may be useful biomarkers for disease progression in MS.
IMO persistently high cortisol levels as a result of the hypersecretion may be bad for MS. Glutamate toxicity and intracellular Ca2+ concentrations have recently gotten some attention in MS research. Here’s an abstract I’ve posted a couple of times I think. Estrogens Attenuate and Corticosterone (Cortisol) Exacerbates Excitotoxicity, Oxidative Injury and Amyloid Beta-Peptide Toxicity in Hippocampal Neurons (in rats)
Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid beta-peptide (A beta) toxicity….
In contrast, corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and A beta.
Estrogens and progesterone also attenuated A beta- and glutamate-induced elevation of intracellular free Ca2+ concentrations.
I think corticosterone is the stress hormone cortisol. Although this is not MS research, this abstract, The Possibility of Neurotoxicity in the Hippocampus in Major Depression: A Primer on Neuron Death
reinforces a connection between hypersecretion of cortisol, glutamate excitotoxicity and Ca2+ concentrations in the loss of neurons, specifically in the hippocampus.
article reviews current knowledge about how hippocampal neurons die during insults, focusing on issues related to the trafficking of glutamate and calcium, glutamate receptor subtypes, oxygen radical generation, programmed cell death, and neuronal defenses.
glucocorticoids, the adrenal steroids secreted during stress, may play a contributing role to any such neuron loss. The subtypes of depression associated with the hippocampal atrophy typically involve significant hypersecretion of glucocorticoids, and the steroid has a variety of adverse effects in the hippocampus, including causing overt neuron loss.
So, I definitely tie the hypersecretion of cortisol (HPA hyperactivity) to neuronal loss. People with MS seem to lose neurons (i.e., brain atrophy) and the HPA hyperactivity has been linked with disease progression in people with MS (per the first abstract). And, while this later abstract is on depression per se and not depression in people with MS, it is generally well known (I think) that many people with MS may also suffer from depression, that may or may not be “co-existing” with MS.
Jaded I hope this helps a tiny bit. It’s a bit about why I’m personally intrigued by the case I posted about chromosome 6 and the hypersecretion of corticotrophins. It seems to me (no scientific or medical background) that hypersecretion of cortisol can cause gluatamate excitotoxicity and neuronal loss. I seriously question if it may be operational in the MS disease process as well. That is a personal opinion only. My cortisol levels were definitely high when I had my hormones tested and I had NO progesterone.
Jaded--as for steroids and MS, I’m happy to learn they’re being studied for MS. Some time ago I posted info that methlyprednisolone dose dependently contributed to axonal loss in rats and interfered with a neuroprotective pathway. Personally, I’m very skeptical of them. They are no longer recommended for use in traumatic brain injuries where inflammation is a major concern.
As to LDN, it’s my understanding that the hypothesis about its mode of action pertains to glutamate excitotoxicity as well.
Brock—I have no biological background and don’t know anyone to lean on either with or without a bias. I agree with Sojourner, we need to do a lot ourselves. If you’re interested in a more scientific take on MS, I’d also recommend the Accelerated Cure Project
. That link is to the news update.
Take care everyone. I do believe there’s progress and that they’re starting to focus in on neurodegeneration and not just inflammation. Another long post I know but I'll back off.