Insulin-like growth factor-I (IGF-I) protects myelination from undernutritional insult: studies of transgenic mice overexpressing IGF-I in brain

Abstract

Using insulin-like growth factor-I (IGF-I)-overexpressing transgenic (Tg) mice as a model, we have shown that IGF-I promotes myelination by increasing the number of oligodendrocytes and stimulating the expression of myelin-specific protein genes. In the present study, we investigated whether IGF-I protects myelination from undernutritional insult in Tg mice. Mice were undernourished beginning from postnatal (P) day 1, a time coincident with the onset of transgene expression, and sacrificed at P20. Consistently with our previous studies, brain weights of undernourished non-Tg control mice were decreased by approximately 18%. Brain weights of undernourished IGF-I Tg mice, however, were the same as those of well-fed control mice and much greater than those of undernourished control mice. The expression of two major myelin proteins [myelin basic protein (MBP) and proteolipid protein (PLP)] in cerebral cortex (CTX) and hippocampus (HIP) was decreased by 73-92% in undernourished control mice, as judged by Northern and Western blot hybridization. The abundances of MBP and PLP mRNAs and proteins, however, were decreased by only 40-70% in undernourished IGF-I Tg mice. To assess the number of oligodendrocytes and their precursors, antibodies specific for carbonic anhydrase II (CAII; an oligodendrocyte marker) and NG2 (a precursor marker) were used. Compared to their well-fed counterparts, undernourished control mice exhibited 17-30% decreases in the number of oligodendrocytes and their precursors in CTX and corpus callosum (CC), whereas well-fed IGF-I Tg mice had 21-35% increases in CTX and CC. Undernourished IGF-I Tg mice exhibited cell numbers similar to those of well-fed control mice. These data indicate that IGF-I protects myelination from undernutrition damage during development.