The effect of stress on the neuropathogenesis of Theiler's virus-induced demyelination as an animal model of multiple sclerosis
Year: 2006
Type: dissertation
Abstract: Stressful life events have been associated with the onset and/or exacerbation of\nmultiple sclerosis (MS). To investigate the effects of stress on the pathogenesis of MS,\nwe employed restraint stress (RST) in the Theiler’s virus-induced demyelination\n(TVID) model, an animal model for human MS. Intracerebral inoculation of\nsusceptible strain of mice with Theiler’s murine encephalomyelitis virus (TMEV)\nresults in a biphasic disease – an acute encephalomyelitis and chronic demyelination.\nThe establishment of persistent viral infection is critical in inducing immune-mediated\ndemyelination during the chronic disease. The exposure of mice to RST prior to viral\ninfection produced a stress response as evidenced by elevated circulating corticosterone\n(CORT). To further study the effect of stress on the immune response to TMEV\ninfection and demyelination, we first examined the cytokine and chemokine response\nduring the acute TMEV infection. We demonstrated that RST down-regulated the\nvirus-induced expression of chemokines, Ltn, IP-10, RANTES, and pro-inflammatory\ncytokines, TNF, IFN and LT in both the brain and spleen during early infection.\nHistologically, a decreased pattern of inflammation was observed in the brain of\nrestrained mice as compared to non-restrained mice. The increased viral titer was noted in the CNS of restrained mice and was correlated with the decreased production\nof pro-inflammatory cytokine, suggesting an impaired immune response by RST.\nSecondly, the duration of stress on the late demyelination was investigated. Repeated\nand chronically stressed SJL/J mice developed an early onset of clinical signs and a\ndelayed onset was observed in acutely stressed mice. Both acute and chronic RST\nsuppressed the antibody response to TMEV and stressed displayed a higher incidence\nof demyelination than non-restrained mice. Axonal loss was also noted in chronic\nstressed mice. Additionally, RST caused an increased systemic viral infection in\nextraneural organs during the acute infection and cardiotropic TMEV was isolated\nfrom the heart of stressed mice. Taken together, stress resulted in profound\nimmunsuppression during acute infection, which may consequently increase the\nincidence of demyelination. The present study may be generalized in human MS\nwhich is potentially triggered by viral infection.
Author: Wentao Mi
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G840426220
OpenAlex ID: W2307179522