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Abstract

The Effects of Acute and Chronic Stress on Late Stage Theiler's Virus Induced Demyelination

1Chaffee, B.K., 1&2Young, C.R., 1Hart, C., 1Alford, E., 1Steelman, A., 1Dean, D., 2Meagher, M.W., and 1Welsh, C.J.R.

1 Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine;

2 Department of Psychology, College of Liberal Arts,

Texas A&M University, College Station, TX 77843

Background-

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS), affecting 1 in every 2000 people in the United States. Inflammation, autoimmune demyelination, and axonal damage are characteristic of MS lesions. Clinical signs include spastic paralysis, tremors, ataxia, optic neuritis, and incontinence (1). At least two distinct types of MS occur. Over 80% of cases are the remitting-relapsing type which often leads to the second type, chronic progressive. The cause of MS is unknown, but genetic factors have been shown to play a significant role while they are clearly not the only factor involved (2).  A viral etiology for MS has also been proposed, although no virus has been definitively and solely identified in MS.  However, much of the epidemiological data on MS implicates viruses as one potential cause of MS. After the British introduction of canine distemper virus to the Faroe islands, there was an increased incidence of MS there (3). Many of the animal models for MS have a viral etiology, including Theiler's murine encephalomyelitis virus (TMEV) infection in mice.

TMEV is a naturally occurring, single stranded RNA Cardiovirus in the family Picornaviridae that causes neurological and gastrointestinal disease in certain strains of mice. Two distinct subtypes of TMEV have been identified. The first subtype, which includes the GDVII strain, is extremely neurovirulent with a high mortality rate.  The second subtype, including the BeAn strain, induces an acute encephalitis followed by a chronic, demyelinating phase when the virus persists (4). It is the late, chronic, demyelinating phase that most closely resembles MS. Extensive lesions in the white matter of the CNS with mononuclear cell infiltration is characteristic of this phase. Different strains of mice have varying susceptibility to TMEV due to H-2D class I haplotypes (5). SJL mice are one of the susceptible strains that develop the chronic, demyelinating phase of TMEV. 

Psychological stress plays a significant role in the onset and recurrence of MS in humans. Stress has been defined many ways, but it is any occurrence that attempts to upset the homeostatic balance of an organism. Acute stress that lasts minutes to hours has been shown to stimulate immune function, while chronic stress that lasts for weeks or months has been shown to suppress immune function (6). These effects are mediated by interactions between the endocrine, immune and nervous systems. Chronic restraint stress prior to infection with TMEV increases mortality in susceptible strains of mice.  In this model, stress activates the hypothalamic pituitary-adrenal (HPA) axis and the autonomic nervous system, which results in immunosuppression mainly through the increased production of glucocorticoids (7). The effects of restraint stress on the late disease have yet to be fully investigated.

Objective-

We studied the effects of acute and chronic restraint stress on the chronic demyelinating phase of TMEV in SJL mice by comparing viral titers, autoantibody titers, and histological lesions in different experimental groups. We hope to determine how different types of stress affect the progression of the disease as a model for MS.