No abstract

Multiple sclerosis (MS) is a devastating CNS disease of unknown origin. Multiple factors including genetic background, infection, and psychological stress affect the onset or progression of MS. Theiler's murine encephalomyelitis virus (TMEV) infection is an animal model of MS in which aberrant immunity leads to viral persistence and subsequently results in demyelination that resembles MS. Here, we examined how stress during acute TMEV infection altered virus-specific cell mediated responses. Using immunodominant viral peptides specific for either CD4+ or CD8+ T cells, we found that stress reduced IFN-γ producing virus-specific CD4+ and CD8+ T cells in the spleen and CD8+ T cells CNS. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus or viral peptides, indicated that stress decreased both type 1 and type 2 responses. Glucocorticoids were implicated in the decreased T cell function as the effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone. As T cells mediate viral clearance in this model, our data support the hypothesis that stress-induced immunosuppression may provide a mechanism for enhanced viral persistence within the CNS.

No abstract

Previous studies have established a link between adverse early life events and subsequent disease vulnerability. The present study assessed the long-term effects of neonatal maternal separation on the response to Theiler's murine encephalomyelitis virus infection, a model of multiple sclerosis. Balb/cJ mouse pups were separated from their dam for 180-min/day (180-min MS), 15-min/day (15-min MS), or left undisturbed from postnatal days 2–14. During adolescence, mice were infected with Theiler's virus and sacrificed at days 14, 21, or 35 post-infection. Prolonged 180-min MS increased viral load and delayed viral clearance in the spinal cords of males and females, whereas brief 15-min MS increased the rate of viral clearance in females. The 15-min and 180-min MS mice exhibited blunted corticosterone responses during infection, suggesting that reduced HPA sensitivity may have altered the immune response to infection. These findings demonstrate that early life events alter vulnerability to CNS infection later in life. Therefore, this model could be used to study gene-environment interactions that contribute to individual differences in susceptibility to infectious and autoimmune diseases of the CNS.

Pain reactivity is often assessed in rodents by measuring the latency of tail withdrawal from radiant heat (the tail-flick test). Using this test, the authors show that the magnitude of antinociception observed in spinal rats depends on test location; antinociception is observed at, and distal to, where shock is applied, but not at more proximal sites (Experiments 1 & 2). Experiment 3 evaluates the generality of this observation by testing 3 other shock schedules that are known to elicit distinct forms of antinociception. In all but 1 case, the magnitude of antinociception varied as a function of test location. Experiment 4 shows that morphine also has a greater impact at distal test locations. Experiment 5 assessed the impact of tailshock on reactivity to radiant heat applied to the foot. Of the 5 distinct forms of shock-induced antinociception studied, only 2 produce a robust antinociception at this test location.