A novel microtubule-associated protein-2 expressed in oligodendrocytes in multiple sclerosis lesions

Elucidation of the mechanisms involved in the regeneration of oligodendrocy tes and remyelination is a central issue in multiple sclerosis (MS) researc h. We recently identified a novel alternatively spliced, developmentally re gulated oligodendrocyte-specific protein designated microtubule-associated protein-2 + 13 [microtubule-associated protein-2 expressing exon 13 (MAP-2 + 13)]. MAP-2 + 13 is expressed in human fetal oligodendrocytes during proc ess extension and myelination but is minimally expressed in normal mature C NS. To test the hypothesis that MAP-2+13 is reexpressed in regenerating oli godendrocytes in MS lesions, we examined the brains of MS patients for the expression of this protein. By immunocytochemistry using a series of monocl onal antibodies specific for MAP-2 + 13, we determined that MAP-2 + 13 expr ession was up-regulated in all 31 lesions from 10 different MS brains. MAP- 2 + 13 was expressed in regenerating oligodendrocytes associated with demye linated lesions, with the highest counts found in regions of extensive remy elination. By electron microscopy, MAP-2 + 13 was localized to oligodendroc ytes engaged in remyelination, evident by their process extension and assoc iation with thinly myelinated (remyelinated) and demyelinated axons. These results suggest a hitherto unsuspected role for this microtubule-associated protein in oligodendrocyte function during development and myelin repair.