Pathology of dysmyelination and demyelination

New York University School Of Medicine, New York NY

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): The myelin sheath/axon complex in the vicinity of the node of Ranvier of myelinated fibers is a precisely organized structural unit believed to have evolved to optimize rapid and efficient nerve conduction. The principal components are a very large and uniquely structured axoglial junction, which separates nodal sodium channels from internodal potassium channels. Minor damage to this intricate nodal/paranodal complex could significantly affect nerve conduction and cause functional losses, even with changes subtle enough to escape detection by routine methods. In view of the potential functional significance of "subtle" pathological changes in this complex, we wish to define them more fully in experimental models in which the pathogenetic elements can be controlled and in which we can analyze the pathology using not only classical light microscopic and ultrastructural techniques but also ultrastructural immunocytochemistry in conjunction with freeze-fracture methodology. We will make use of mutations affecting myelinated nerve fibers to assess the effects of specific deficiencies on the integrity of the axoglial junction, on the density and distribution of the nodal and internodal ion channel aggregates, on nerve conduction and on axon damage. We will also use the in vivo model of focal antibody-mediated dysmyelination and demyelination, which we have been working with, to determine whether equivalent abnormalities can be identified in this model of multiple sclerosis. [unreadable] [unreadable]