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

摘要

The objective of these studies is to examine the impact of signaling by neuregulin family members in a mouse model of virus induced demyelination. These studies utilize intraspinal cord injection of Theiler's murine encephalomyelitis virus (TMEV) into mice. The hypothesis tested in these studies is that increased erbB-mediated signaling will have a protective effect in this model of multiple sclerosis (MS), and that decreased erbB-mediated signaling will have a deleterious affect on the animals. Pharmacological agents, recombinant viruses and knockout mice are being used to test this hypothesis. The data described herein suggest that within the spinal cords of mice injected with TMEV the induction of IL-11 may be a key mediator of oligodendrocyte health and well being and this may represent the mechanism for increased myelin basic protein (MBP) mRNA that is reported. Furthermore, erbB3, a receptor for the neuregulins is highly expressed by cells infiltrating the central nervous system (CNS).