Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination

Metabolic insult results in apoptosis and depletion of mature oligodendrocy tes during demyelination. To examine the role of insulin-like growth factor -1 (IGF-1) during acute demyelination and remyelination in the adult CNS, w e exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cup rizone intoxication. Demyelination was observed within the corpus callosum in both wild-type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wi ld-type mice showed significant apoptotic mature oligodendrocytes and a dra matic loss of these cells within the lesion that resulted in near complete depletion and demyelination by week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was near full recovery by week 5. This rapid recovery was apparently caused by survival of the mature oligodendrocyte p opulation because apoptosis was negligible, and by week 4, the mature oligo dendrocyte population was completely restored. Furthermore, despite demyeli nation in both wild-type and IGF-1 tg mice, oligodendrocyte progenitors acc umulated only in the absence of mature oligodendrocytes and failed to accum ulate if the mature oligodendrocytes remained as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be important in preventing th e depletion of mature oligodendrocytes in vivo and thus facilitates an earl y recovery from demyelination.