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Parkinson’s Disease, Stress, and Inflammation

May 13, 2011

A report in this morning’s Science Daily News started a cascade of  its own as several pieces of the puzzle clicked into place. With the charming title of

“Seeing Family for the Holidays? Scientists Discover How the Stress Might Kill You”

It goes on to state “”…. researchers from the University of Connecticut Health Center have found that the same part of our nervous system that is responsible for the fight-or-flight response (called the sympathetic nervous system) also controls regulatory T cells, which are used by the body to end an immune response once a foreign invader has been removed or destroyed.”

So, here is a link between the endocrine system’s fight or flight response and the immune system’s method of ending an immune response (which fails in the case of PD) with the nervous system’s sympathetic division being responsible for both.  Is it possible that events impacting the endocrine stress system could act upon the sympathetic nervous system in such a way as to impinge upon its ability to end an immune response that is no longer needed?

Looking a little further – it is often reported that people experienced traumatic events in the couple of years prior to their first PD symptoms. How does trauma affect regulatory T cell populations and thereby the control of the immune system’s ability to halt an inflammatory response? That question led to this:

Brain Behav Immun. 2009 Nov;23(8):1117-24. Epub 2009 Jul 18.

Substantial reduction of naïve and regulatory T cells following traumatic stress.

Sommershof A, Aichinger H, Engler H, Adenauer H, Catani C, Boneberg EM, Elbert T, Groettrup M, Kolassa IT.

Division of Immunology, University of Konstanz, Konstanz, Germany.

Posttraumatic stress disorder (PTSD) is associated with an enhanced susceptibility to various somatic diseases. However, the exact mechanisms linking traumatic stress to subsequent physical health problems have remained unclear. This study investigated peripheral T lymphocyte differentiation subsets in 19 individuals with war and torture related PTSD compared to 27 non-PTSD controls (n=14 trauma-exposed controls; n=13 non-exposed controls). Peripheral T cell subpopulations were classified by their characteristic expression of the lineage markers CD45RA and CCR7 into: naïve (CD45RA(+) CCR7(+)), central memory (T(CM): CD45RA(-) CCR7(+)) and effector memory (T(EM): CD45RA(-) CCR7(-) and T(EMRA): CD45RA(-) CCR7(-)) cells. Furthermore, we analyzed regulatory T cells (CD4(+)CD25(+)FoxP3(+)) and ex vivo proliferation responses of peripheral blood mononuclear cells after stimulation with anti-CD3 monoclonal antibody. Results show that the proportion of naïve CD8(+) T lymphocytes was reduced by 32% (p=0.01), whereas the proportions of CD3(+) central (p=0.02) and effector (p=0.01) memory T lymphocytes were significantly enhanced (+22% and +34%, respectively) in PTSD patients compared to non-PTSD individuals. To a smaller extent, this effect was also observed in trauma-exposed non-PTSD individuals, indicating a cumulative effect of traumatic stress on T cell distribution. Moreover, PTSD patients displayed a 48% reduction in the proportion of regulatory T cells (p<0.001). Functionally, these alterations were accompanied by a significantly enhanced (+34%) ex vivo proliferation of anti-CD3 stimulated T cells (p=0.05). The profoundly altered composition of the peripheral T cell compartment might cause a state of compromised immune responsiveness, which may explain why PTSD patients show an increased susceptibility to infections, and inflammatory and autoimmune diseases.

PMID: 19619638 [PubMed – indexed for MEDLINE]

So here we have T cells, essential for communication of stand down orders within the immune system, suffering a 50% reduction in population due to trauma. If the unfortunate individual was one with an unusual sensitivity to bacterial toxin LPS due to early life events and was barely able to control the microglia anyway, what does a loss of half his communication ability do?

And what does this say about the rather large sub-group of PWP who report unusually traumatic childhoods? If they had also experienced LPS hypersensitivity, would they not have a similar problem?

Stress (trauma) reduces the ability of the sympathetic nervous system to regulate immune response which, in turn, allows the runaway microglial activation that ultimately damages the substantia nigra and reduces motor symptoms.

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