Spreading depression transiently disrupts myelin via interferon-gamma signaling.

Spreading depression transiently disrupts myelin via interferon-gamma signaling.
Exp Neurol. 2014 Dec 8;
Authors: Pusic AD, Mitchell HM, Kunkler PE, Klauer N, Kraig RP
Abstract
Multiple sclerosis and migraine with aura are clinically correlated and both show imaging changes suggestive of myelin disruption. Furthermore, cortical myelin loss in the cuprizone animal model of multiple sclerosis enhances susceptibility to spreading depression, the likely underlying cause of migraine with aura. Since multiple sclerosis pathology involves inflammatory T cell lymphocyte production of interferon-gamma and a resulting increase in oxidative stress, we tested the hypothesis that spreading depression disrupts myelin through similar signaling pathways. Rat hippocampal slice cultures were initially used to explore myelin loss in spreading depression, since they contain T cells, and allow for controlled tissue microenvironment. These experiments were then translated to the in vivo condition in neocortex. Spreading depression in slice cultures induced significant loss of myelin integrity and myelin basic protein one day later, with gradual recovery by seven days. Myelin basic protein loss was abrogated by T cell depletion, neutralization of interferon-gamma, and pharmacological inhibition of neutral sphingomyelinase-2. Conversely, one day after exposure to interferon-gamma, significant reductions in spreading depression threshold, increases in oxidat...

Source: Experimental Neurology - December 8, 2014 Category: Neurology Authors: Pusic AD, Mitchell HM, Kunkler PE, Klauer N, Kraig RP Tags: Exp Neurol Source Type: research