A role for oligodendrocyte-derived IGF-1 in trophic support of cortical neurons

Neurons and glia interact in the development of mammalian central nervous s ystems and in the maintenance of stable myelinated axons. Recent evidence s uggests a role for oligodendrocytes in providing trophic support for neuron s during development and in the mature nervous system. This work prompted u s to study oligodendrocyte influences on neuronal survival and death in vit ro. Rat embryonic cortical neurons were co-cultured with purified oligodend rocytes at different developmental stages and separately with oligodendrocy te-conditioned medium. Neuronal survival was measured by immunocytochemistr y and H-3-GABA uptake. Neurons show a marked increase in survival when co-c ultured directly with oligodendrocyte precursors (OPCs) and differentiated oligodendrocytes. Neurons cultured in the presence of OPCs separated by a p ermeable membrane and those cultured in medium conditioned by oligodendrocy tes also show a significant increase in survival. Medium conditioned by dif ferentiated oligodendrocytes provides a greater survival effect than medium conditioned by OPCs. Neutralising antibodies to IGF-1, but not to other ca ndidate trophic factors, block the soluble survival effect of oligodendrocy tes. Cells of the oligodendrocyte lineage produce IGF-1 and recombinant IGF -1 promotes neuronal survival under identical conditions. This study provid es evidence that OPCs and differentiated oligodendrocytes support neuronal survival by both contact-mediated and soluble mechanisms and that IGF-1 sig nificantly contributes to this effect. (C) 2001 Wiley-Liss, Inc.