ASTROCYTES INHIBIT SCHWANN-CELL PROLIFERATION AND MYELINATION OF DORSAL-ROOT GANGLION NEURONS IN-VITRO

Schwann cells promote the regrowth of nerve fibers in both the PNS and CNS and might thus be of value in strategies to promote repair follow ing injury or demyelination in the CNS. The effectiveness of Schwann c ells in promoting repair could, however, be limited by interactions wi th reactive astrocytes that are prominent at lesioned and demyelinated sites. To investigate this possibility, experiments were performed to determine the influence of cortical astrocytes an Schwann cell prolif eration and myelination of dorsal root ganglion (DRG) neurons in vitro . DRG neurons from embryonic rats and Schwann cells, astrocytes, and f ibroblasts isolated from the sciatic nerve, cerebral cortex, and crani al periosteum, respectively, of neonatal rats were purified and then r ecombined to provide neuron-Schwann cell, neuron-Schwann cell-astrocyt e, and neuron-Schwann cell-fibroblast cultures. Astrocytes inhibited b oth neuron-dependent Schwann cell proliferation and the myelination of axons by Schwann cells. The expression of galactocerebroside, but not of the 04 antigen, was inhibited by astrocytes, suggesting that astro cytes blocked Schwann cell differentiation prior to the onset of myeli nation. Ultrastructural analysis of the cultures also indicated that b oth axonal ensheathment and the segregation of large axons into 7:1 re lationships were decreased in the presence of astrocytes. Astrocytes d id not affect the expression of the basal lamina components type IV co llagen and laminin, and basal lamina formation assessed by electron mi croscopy was only slightly decreased. Some of these inhibitory effects appear to be mediated by diffusible factors since astrocyte-condition ed medium also reduced Schwann cell myelination. Fibroblasts or fibrob last-conditioned medium did not induce such inhibitory effects, indica ting that the effects were astrocyte specific. We conclude that cortic al astrocytes release a soluble factor(s) that inhibits specific aspec ts of neuron-Schwann cell interactions leading to myelination.