MYELINATION AND REMYELINATION OF AGGREGATE RAT-BRAIN CELL-CULTURES ENRICHED WITH MACROPHAGES

We reported previously that accumulation of myelin basic protein (MBP) in foetal brain aggregate cultures is enhanced by supplementation wit h peritoneal macrophages. The present study demonstrates that the rate of MBP accumulation in macrophage-enriched cultures continues to incr ease over time unaccompanied by a matching increase in the oligodendro cyte marker cyclic nucleotide phosphodiesterase, while that of control cultures reaches a plateau, These observations are supported by elect ron microscopic evidence of cumulative numbers of myelinated axons in the aggregates over time and by enhanced expression of myelin protein genes in macrophage-enriched relative to control cultures, Aggregates demyelinate following short-term exposure to cytokines and antimyelin oligodendrocyte glycoprotein antibody, and MBP synthesis resumes follo wing removal of demyelinating agents, Supplementation of cultures with macrophages influences the degree of myelin breakdown and remyelinati on, drawing attention to the role that macrophage-derived growth facto rs may play in myelinogenesis and myelin repair in inflammatory demyel inating disease. (C) 1997 Wiley-Liss, Inc.