Long term survival of chronically demyelinated axons in the taiep rat

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS in which neuroaxonal loss underlies permanent neurological disability. Axon loss in MS has been attributed to several causes, including loss of trophic/metabolic support from the myelin sheath. However, the contribution of chronic demyelination to axonal demise has been difficult to ascertain, due largely to the lack of long-lived models and uncertainty about the location of the primary injury site in long fibre tracts in MS patients. Here, we examine chronically demyelinated axons using light and electron microscopy of spinal cord tracts of 1- to 24-month-old taiep rats, in which the gene that is mutated, Tubb4a p.A302T, is expressed highly in oligodendrocytes. We find that small diameter axons in the dorsal column can survive for many months following demyelination. This is associated with significantly increased densities of oligodendroglia, and supernumerary glial cell processes. We hypothesise that trophic and metabolic support, sufficient to support axon survival, can be achieved through close contact between axons and glia. While efforts to restore myelin in MS remain crucial to recovering normal neurological function, myelin per se might not be a prerequisite for axonal survival under all circumstances.