How Chronic Stress Worsens Neurodegenerative Disease Course

[Frank]

Link

--Frank

[TwistedHelix]

Thanks for that interesting link Frank. I had a quick look at one of the related links, " stress response prevents neurodegeneration", and got a bit of a surprise: it seems that interferon gamma, of all things, can be neuro protective. It all depends on timing and balance, and just goes to show how damned complicated this human machine is – just when you think you "know" something is good for you, or bad for you, some piece of research pops up which says, " it all depends" – on timing; on quantity; on the presence or absence of other substances.
I don't know if stress can ever be good for you, but at least we have evolved to be able to cope with sudden, short, sharp threat: it's the long, grinding, chronic strain of modern living which seems to be so bad for our us,

[finn]

Dom,
like the study behind Frank's link shows, it is stressful for both mice and men to face an unknown and aggressive male. But what comes to interferon-gamma, there might be a difference between the two species. Back in the 80s researchers were able to cure EAE mice with interferon-gamma, but in humans it just made their MS worse.

-finn

[gwa]

Researchers were also able to give mice more leptin to make them lose weight in the 90's and they thought the same process would apply to humans.

Unfortunately they found out that fat people had an overabundance of leptin, so this is just another area where mice and men are different.

gwa

[TwistedHelix]

I think what particularly struck me was that on one page was an article saying, in a nutshell, " stress is bad", yet contained the link to an article saying, " stress is good" – both of which referred to studies on mice.
This sentence: "the timing of IFN-gamma expression in the brain and the extent of the stress response in the ODCs are factors determining whether or not IFN-gamma has a protective or detrimental effect on EAE." encapsulates for me how a single substance can be both harmful and helpful depending on how and when it is used.
Of course you're right, gwa, mice are very different from human beings, (for example, I almost NEVER crap in the corner of my living room), and I lament the fact that we have to use them at the moment, but for now it's the best we can do. I daren't even think of the potential treatments that have been abandoned because they failed in animals but could actually have worked for us. Like thalidomide, which was a pariah for years but has come back in from the cold as a miraculous treatment for leprosy amongst other things, interferon gamma might turn out to be beneficial if used in a very, very precise way. If not exactly that, then perhaps some other substance which is currently regarded as " bad".
Even the model of chronic stress might be a poor one: I imagine it's pretty hard to get a mouse to worry about its career prospects or failed relationships, but at least the artificial stress might be used as a pointer to physiological responses,

[Lyon]

When looking at the past of MS research it's obvious why the push has been to prove everything scientifically and get away from beliefs based on "it seems like", but there also has to be a middle ground.

I mean, look at the situation in the world of MS. Science hasn't been able to prove anything scientifically, yet along the way common sense and logic have become scorned because they aren't provable scientifically.

In the absence of scientific fact.....until proven otherwise, I think common sense and logic should be the default and logic makes it obvious that chronic stress isn't a favorable situation.

Bob

[Shayk]

Frank--thanks for posting this. I’ve had a keen interest in the stress hormone “cortisol” and can’t let this pass without some comments from another perspective.

While that article clearly focuses on stress and the immune system, I think it’s worthwhile to point out that the stress hormone “cortisol”, at persistently high levels is also neurotoxic (glutamate toxicity). High cortisol levels, already linked to cognitive and physical disability as well as disease progression in people with MS, can also result in symptoms people with MS may experience.

The background info from this clinical trial (not an MS trial) illustrates that quite well I think. Tylenol for Mood and Memory Changes Associated With Corticosteroid Therapy

If you read it you’ll see that prolonged prednisone (synthetic cortisol) use in people without MS is associated with deficits in cognitive functioning (memory and others), major depression and hippocampal atrophy. (Muu--it mentions lamotrigine too)

With respect to hippocampal atrophy in people with MS, here’s info from the AAN meeting
Regional Hippocampal Atrophy in Relapsing Remitting and Secondary Progressive Multiple Sclerosis

Nancy L. Sicotte, Kyle Kern, Barbara Giesser, Amrapali Arshanapalli, Alison Burggren, Susan Bookheimer, Los Angeles, CA

CONCLUSIONS/RELEVANCE: Selective volume loss occurs within the hippocampus in MS. Changes appear first in the CA1 subregion and then spread to the other CA fields and the dentate gyrus. The volume changes that occur are disproportionate to global brain volume loss. Glutamate toxicity or other systemic insults may account for these changes.

With respect to depression and hippocampal atrophy (not people with MS), here’s an interesting abstract:
The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death

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

All of this to say, I think there may be more to “stress” than how it impacts the immune system in people with MS and one of the questions yet to be answered in MS research is whether or not the high levels of cortisol in people with MS contribute to “our” cognitive problems, depression and hippocampal atrophy, just like it apparently does for people without MS.

Dom/Finn—I couldn’t find any links to the other info you cited (that’s ok) Dom, you might be interested in this info. Protective and damaging effects of stress mediators: central role of the brain

Lyon—I agree with you.

chronic stress isn't a favorable situation.

But I'd add, and neither are high levels of the stress hormone "cortisol".

Take care all—looks like relaxation is “in”.

Sharon

[TwistedHelix]

Thanks for those great links Sharon: the definition of " Allostatic load" is spot on and very useful to know. If you're interested, the link I was referring to was on the right hand side of the page under the heading "related science stories", on the page Frank linked to in his original post on this thread.

Relaxation? Relaxation!! Chance would be a fine thing! I've just found out that my Visa card has been used in France, Taiwan and America for HUNDREDS of pounds. I'm just going to check my bank statements to see if I bought myself a good time.

[Lyon]

Man, that's an awful thing to hear! You don't seem too upset about it so I assume you are aware that the most you can be held responsible for in the case of fraudulent use is $50.00, at least here in the US.
Bob