Citation

Multiple sclerosis (MS) is a chronic inflammatory a utoimmune disease that destroys central nervous system (CNS) myelin. Although, the exact pa thophysiology of MS is unknown, it is associated with CNS infiltration of T-cells and mon ocytes, which subsequently activate phagocytic cells that directly damage myelin. Brai n-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor (TrkB ), have recognized roles in myelin structure formation, maintenance, and repair. We us ed an experimental autoimmune encephalomyelitis (EAE) model of MS to determine ch anges in TrkB expression that may contribute to neurological recovery and myelin repa ir following an early inflammatory immune-mediated attack on CNS myelin. Spinal cord ( SC) TrkB gene and protein expression were analyzed at various time intervals post-EAE in duction. Analysis of gene and protein expression was conducted in animals with EAE relati ve to active controls (AC) and nave controls (NC). We showed significant increases in T rkB protein in the SC of EAE rats 12 days post-induction relative to controls. This elevated TrkB expression correlated with the onset of neurological recovery days 12 to 15 post-EAE induct ion. Furthermore, immunohistochemistry (IHC) analysis revealed up-regulated expression of TrkB in several SC cell types including a specific subset of BDNF responsive neuronal cells. Finally, transmission electron microscopy (TEM) showed the ultrastructural integrity of myeli n is already compromised during the early, inflammatory stage of EAE prior to widespread demye lination. Therefore, the molecular signaling of SC BDNF via TrkB represents a key ther apeutic target whose manipulation could facilitate myelin repair and neurological recovery following an MS-induced myelin attack.