Myelin-associated inhibitors of neurite growth

CNS myelin and oligondendrocyte membranes contain two minor proteins with strong inhibitory effects on growing neurites (neurite growth inhibitors NI-35 and NI-250). Monoclonal antibodies (IN-1, IN-2) were obtained that neutralize this activity in a variety of culture assays including adult rat optic nerve explants, which are invaded by growing neurites under the influence of these antibodies. In vivo, corticospinal tract lesions in young rats are known to be followed by abortive sprouting, not exceeding 1 mm of elongation. In contrast, the presence of antibody IN-1 led to regrowth of corticospinal axons over more than 5 mm within 2-3 weeks. In development, a negative guidance or channeling function may be associated with these inhibitors for late growing CNS tracts. In fact, application of antibodies or absence of oligodendrocytes during the first postnatal week led to severe anatomical disturbance of the developing rat corticospinal tract. Additional, e.g., stabilizing functions for these inhibitors in the adult CNS remain to be investigated.