Differential effects of stress on a murie model of multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a demyelinating autoimmune disease that affects the central nervous system (CNS) in humans. Several studies have shown a strong correlation between stressful events and the onset and exacerbation of MS in patients. Based on this information, similar studies have been undertaken in mice. CNS demyelination is induced in mice by infecting them with Theiler’s murine encephalomyelitis virus (TMEV). After the initial encephalitis phase, the virus persists in susceptible mice strains and demyelination of the CNS occurs, creating a useful model of MS. Using this model, several types of stress – social, restraint, and handling – have been utilized, either prior to infection or concurrently, to study the effects in virus-induced demyelination in mice. However, these studies have primarily focused on the effects of chronic stress, while the effects of acute stress on a MS model have, for the most part, been ignored. The objectives of this experiment are to examine the differences in immune response between chronically and acutely stressed mice. Mice in the acute stress group are hypothesized to experience an enhanced immune response, which should lead to: better viral clearance, smaller and fewer lesions in the CNS, and better physical coordination than the chronic stress group. Mice will be separated into three groups. One group will undergo chronic stress, another will undergo acute stress, and the last group will serve as the control. Mice will be infected with TMEV and monitored for effects. Weight measurements and behavioral scoring will be utilized as a way of monitoring disease progression in live mice. Continual monitoring will continue as TMEV is allowed to persist into the chronic, demyelinating phase. The mice will be terminated to collect tissue and serum samples during this phase. Since studies comparing immunological effects of acute versus chronic stress have consistently shown that immunosuppression is associated with chronic stress, while immunoenhancement is associated with acute stress, polar results are also expected in this experiment. Following TMEV infection and subsequent CNS demyelination, different results between the chronically and acutely stressed mice seem likely