SCHWANN-CELL INVASION OF THE CENTRAL-NERVOUS-SYSTEM OF THE MYELIN MUTANTS

Schwann cells are excluded from the CNS during development by the glia l limiting membrane, an area of astrocytic specialisation present at t he nerve root transitional zone, and at blood vessels in the neuropil. This barrier, however, can be disrupted and, with the highly migrator y nature of Schwann cells, can result in their invasion and myelinatio n of the CNS in many pathological situations. In this paper we demonst rate that this occurs in a number of myelin mutants, including the mye lin deficient (md) and taiep rats and the canine shaking (sh) pup. Whi le it is still relatively uncommon in the rodent mutants, the sh pup s hows extensive Schwann cell invasion along the neuraxis. This invasion involves the spinal cord, brain stem, and cerebellum and increases in amount and distribution with age. In situ hybridisation studies using a P-0 riboprobe suggest that the likely origin of these cells in the sh pup is the nerve roots, primarily the dorsal roots. Paradoxically, Schwann cell myelination of the CNS increases with time in the sh pup despite a marked, progressive gliosis involving the glia limitans and neuropil. Thus the mechanism by which these cells migrate into the CNS through the gliosed nerve root transitional zone or from vasa nervoru m remains unknown. Extensive Schwann cell CNS myelination may have the rapeutic significance in human myelin disease.