Myelin repair in the central nervous system has been demonstrated in both experimental models and human studies as a normal physiological response to myelin injury. However, in chronic inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), myelin repair is usually incomplete. Previous work in our lab has shown that remyelination can be increased four fold by in vivo administration of monoclonal antibodies directed against undetermined CNS antigens. This remyelination promotion is seen in both immune-mediated and toxic-traumatic models of MS. One possible mechanism by which the antibodies may mediate remyelination is through binding to a unique receptor on oligodendrocytes or glial progenitor cells. This receptor binding may mimic normal signals that induce or coordinate myelination. Many signal transduction cascades involve intracellular calcium changes. In order to investigate the possibility that remyelination promoting antibodies directly activate glial cells, we will use ratiometric fluorescent monitoring of intracellular calcium concentrations ([Ca2+]i). The proposed research will characterize the potential of remyelination promoting antibodies to physiologically activate CNS cells, determine the cell phenotypes involved and the contribution of differentiation state. Specific aim two will utilize phamacological and biochemical techniques to begin to elucidate the intracellular signal transduction components stimulated by the remyelination promoting antibodies.