The Influence of Platelet-derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

Title: THE INFLUENCE OF PLATELET-DERIVED GROWTH FACTOR AND FIBROBLAST GROWTH FACTOR 2 ON OLIGODENDROCYTE DEVELOPMENT AND REMYELINATION Author: Joshua C. Murtie Ph.D. (2004) Thesis Directed By: Regina C. Armstrong Ph.D. Professor, Department of Anatomy Physiology, and Genetics ABSTRACT: Multiple sclerosis (MS) is a demyelinating disease of the central nervous Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by repeated episodes of autoimmune-mediated demyelination. Symptoms of the disease range from loss of vision to paralysis with each episode resulting in a decreased remyelination response. If remyelination does not occur, bare axons will not be able to function properly either by inefficient saltatory conduction or by degeneration resulting from a lack of myelin. This study examines the effects of growth factors on recovery from demyelination. Specifically, what roles do plateletderived growth factor (PDGF) and fibroblast growth factor 2 (FGF2) play during remyelination of the central nervous system? This question will be addressed using the cuprizone model of demyelination with significant remyelination. The remyelination response in this model will be examined in FGF2 knockout mice as well as PDGF alpha receptor (PDGFαR) heterozygous mice. This study examines the elimination of FGF2 signaling and the reduction of PDGF signaling in an animal model of demyelination with significant remyelination. The current results demonstrate that the predominant role for FGF2 during development and remyelination is that of an inhibitor