New Research Shows How Chronic Stress Worsens Neurodegenerative Disease Course
 

New Research Shows How Chronic Stress Worsens Neurodegenerative Disease Course

18 Aug 2007
http://www.medicalnewstoday.com/articles/80016.php

The evidence is accumulating on how bad stress is for health. Chronic stress can intensify inflammation and increase a person's risk for developing central nervous system infections, neurodegenerative diseases, like multiple sclerosis (MS), and other inflammatory diseases, say researchers presenting at the 115th Annual Convention of the American Psychological Association (APA). These researchers have demonstrated for the first time that stress related increases in central nervous system inflammation are behind the adverse effects of stress in an animal model of MS.

Researchers from Texas A & M University used mice to show what role social stress plays in the immune process to influence the course of an MS like disease. They proposed that stress induced increases of pro inflammatory cytokines, which are proteins that regulate immune and inflammatory functions, inhibit the clearing of a virus and allow the inflammatory process to run amok. Stress, say the authors, may interact with viral infections to increase vulnerability

to diseases such as MS. Meta-analysis of studies investigating the impact of stressful events in patients with MS show an increased risk of worsening symptoms of the disease.

In a series of experiments on mice, the authors showed that increases in a particular cytokine interleukin-6 (IL-6), which is released during stress and regulates the part of the immune system that fights infection can make socially stressed mice vulnerable to MS-like illnesses.

The researchers used a social disruption model (SDR) to simulate social stress for mice and then infected the mice with Theiler's murine encephalomyelitis (TMEV). Infection with TMEV results in an acute infection of the central nervous system followed by a chronic autoimmune disease similar to that seen in humans with MS. Their laboratory has previously shown that exposure to social stress prior to infection exacerbates both the early viral infection and the later autoimmune demyelinating MS-like phase of the disease.

To create a stressful environment, researchers housed three young male mice together for several weeks. After the mice established a stable social hierarchy, researchers introduced an older aggressive male into the residence for a couple of hours. The intruder exhibits aggressive behavior posturing, fighting, wounding, pursuit that results in submissive behaviors and social defeat in the younger resident mice. This procedure was repeated for three consecutive nightly two-hour sessions with one night off, followed by an additional three nightly sessions. To keep the mice from getting used to the intruder, a new intruder was introduced for each session.

What they found was this stress appears to elevate levels of IL-6, which subsequently increases the severity of the MS-like illness. Furthermore, using specific IL-6 neutralizing antibody treatments during the stress exposure can prevent the stress-related worsening of the disease, said the authors.

In one experiment, they showed that mice exposed to social disruption had elevated central and peripheral levels of IL-6. However, infusing the neutralizing antibody into the brain prevented this stress-induced increase in IL-6. This demonstrated that the antibody could effectively reverse the stress-related increases in IL-6 in brain and in circulating blood.

Results from a second experiment showed that administering the IL-6 neutralizing antibody during the stress exposure prevented worsening of the TMEV infection. By blocking the stress-induced elevation of IL-6, TMEV infection was weakened, which lessened some of the disease symptoms, such as motor impairment, inflammation in the brain and spinal cord, and the viral level in the central nervous system. Based on these findings, Dr. Mary Meagher, the lead researcher, proposes that the adverse effects of stress-induced IL-6 on TMEV infection are enough to create a pro-inflammatory environment that interferes with the immune response to infection. Because the early immune response shapes the later specific immune response to infection, impairment of the early response could account for the increased viral level, prolonged viral infection, increased CNS inflammation, and the subsequent exacerbation of the chronic autoimmune disease.

There is a growing body of evidence in both animal and human studies that suggests that exposure to stress can increase and sustain the release of pro-inflammatory cytokines following an assault on the immune system. Thus, the present findings might help scientists unravel which biobehavioral mechanisms offset the adverse health effects of chronic social stress in humans. "Similar to mice exposed to repeated social defeat by an aggressive intruder, people exposed to chronic social conflict experience high levels of stress and consequent dysregulation of the immune system, thereby increasing vulnerability to infectious and autoimmune disease," said Meagher. "The cytokine response during chronic stress appears to play a key role in exacerbating the acute CNS infection and the development of subsequent autoimmune responses."

Furthermore, interventions that prevented or reversed the stress-induced increases in IL-6 in the mouse model may have implications for humans, said Meagher. It is possible that the adverse effects of social conflict on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine. Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressant medication, omega-3 fatty acids, and mindfulness relaxation training. However, human clinical trials are needed to fully evaluate this issue.

Presentation: "Severe or Traumatic Stress and Inflammation in Multiple Sclerosis," Mary W. Meagher, PhD, Texas A&M University

Session 1157 Symposium: Traumatic Stress, Cardiovascular Disease, Metabolic Syndrome, and Neurodegenerative Disease, 11:00 11:50 AM, Friday, August 17, Moscone Center, Second Floor-West Building, Room 2020

The American Psychological Association (APA), in Washington, DC, is the largest scientific and professional organization representing psychology in the United States and is the world's largest association of psychologists. APA's membership includes more than 148,000 researchers, educators, clinicians, consultants and students. Through its divisions in 54 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting health, education and human welfare.

are we paying attention?
 

:) This is what it is all about. And note that it isn't the neurologists leading the charge so don't asume that yours will know all this.

One thing that they haven't picked up on yet is that both cytokines and glucocorticoids can act as neurotransmitters and disrupt normal function almost instantly. That's why we fall apart when stressed.

I'm convinced too Rick
 

Dr. James Parkinson originally considered stress the cause of PD. This was stated last year at the PAN forum by Dr. Langston in his talk. So I guess it isn't completely true to say that PD is not a lifestyle illness.

Stress comes from so many sources - insecurities, worry, overwork, trauma, guilt, anger, and on and on. Stress made me rigid before I had PD.

Eliminating stress is not given much consideration in treatment programs. Medicare should contract people to develop exercise programs for people with chronic illness, complete with transportation.

I'll bet the older and disabled would find themselves hanging out at the rec center instead of in the doctor's offices with aches and pains.

paula

Neurology, Psychiatry, Psychology
 

Parkinson's Disease is an Obssesive-Compulsive Disorder but affecting movement.

Obssesive-Compulsive Disorder is Parkinson's Disease but affecting behaviour.

Tourette' Syndrome is Parkinson's Disease but in reverse.

Parkinson's Disease is Tourette's Syndrome but very advanced.

The answers are there if we only care to look.

Hmmm? Interesting statements.
 

But not enough there to discuss. Could you flesh it out a little?

If anyone is interested in this question and will ignore the construction dust, a graphic depiction can be seen at http://www.parkinsonsonline.org/hypotheses.html
Please come back here for discussion though. The other forums are barely operational.

What I'd like to see...
 

.... is a "group" of people, somewhere on this planet that live relatively stress free, and are "proven" relatively stress free, I dunno, maybe an ethnic group or a subset of wealthy people or some group of people (i can't really see who would qualify as life is tough for just about everybody, imho), and the occurrence of PD determined in this group and compared to a "very stressed" group of people. THis would be interesting.
BTW- I guess you have to be a horse to get a stem cell cure these days:D , did ya'll see that in the news?

acute cool, chronic not
 

From an evolutionary standpoint, we were designed to cope with the sudden rush of a big cat. That is acute stress and the main chemical is adrenaline. Adrenaline comes on fast, does its job, and quickly clears out.

Chronic stress is a different matter and there are few situations in primitive lives that qualify. The main chemical is cortisol and it is long-lived.

As ol cs points out, stress is every where in modern society - chronic stress. The kind that never stops. Rushing, the job, the boss, the spouse, the television, etc. An elevated level of cortisol.

Pregnant women are not spared and the placenta sometimes fails. If it fails during the short time period when a particular group of neurons are forming they will be changed. The result is that the baby's control system is overly sensitized and the system is constantly struggling to maintain balance.