Impact of Erb-B Signaling on Myelin Repair in the CNS Following Virus-Induced Damage

Abstract : The objective of these studies is to examine the impact of erbB-mediated signaling on myelin destruction and repair in a novel model of central nervous system (CNS) demyelination. In these studies, we utilize a model of demyelination triggered by direct injection of Theiler s murine encephalomyelitis virus (TMEV) into the spinal cord. This method of lesioning permits us to precisely identify the age and site of the lesion. We hypothesize that increased erbB-mediated signaling will protect animals from disease. Conversely, reduced signaling will worsen demyelination. Our studies have shown that animals that have been exogenously treated with glial growth factor (GGF; a member of the neuregulin family that binds to erbB receptors) have improved clinical function compared to animals receiving glial growth factor 2 or sensory motor derived factor (other members of the neuregulin family). Data to date suggest that the affect of GGF is likely indirect and does not directly affect myelination. Results to date support a role for microRNAs as mediators of this observation. In addition, EGFR levels are low and do not appear to modulate over the course of infection. Myelinating cells do not appear to undergo proliferation, but rather appear to migrate to the site of damage in mice with conditional erbB2 deletions. It is likely that these cells are Schwann cells.