Insulin-like growth factor-I (IGF-I) protects myelination from undernutritional insult: studies of transgenic mice overexpressing IGF-I in brain.
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.
Ye
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Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220, USA. Ping_Ye@med.unc.edu
Lee
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KH
D'Ercole
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AJ
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002452:Cell Count; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development; D005508:Food Deprivation; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism
D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I