How Chronic Stress Worsens Neurodegenerative Disease Course
- From: dav1936531 <dav1936531@xxxxxxxxxxx>
- Date: Mon, 20 Aug 2007 10:35:30 GMT
Science Daily ? 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
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
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, August 17, 2007
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