Research on the roles of growth factors against the damages of the central nervous system in intra-uterine growth retarded infants

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The aim of this study is to determine the effect of undernutrition-indueed intra uterine growth retardation (IUGR) on the development of myelination and to clarify the role of insulin-like growth factor (IGF)- 1 in developing brain.1. Ontogeny of myelin-associated genes, myelin basic protein (MBP) and proteolipid protein (PLP), and IGF- 1 and IGF-2 genes in the developing rat brain.To clarify.the developing courses of myelination in rat brain, we determined the ontogeny of MBP and PLP genes using Northern blot analyses. These two genes, specific for the oligodendrocytes, are expressed from postnatal day (P) 10 and their expressions gradually increase, reaching their maximum at P25 in cerebrum. Glial fibrillary acidic protein (GFAP), specific for astrocytes, appears to be expressed at P5, earlier than MBP and PLP, and reaches its maximum at P25. In cerebellum, the expressions of these genes are earlier than in cerebrum and more rapidly reach their maximum at P15. IGF-1 is already expressed well at PO and its level is maintained until P15, however, after P20 its level rapidly decreases to faint level in adult. On the contrary, IGF-2 expression is constant through PO to adult.2. Effect of undernutrition-indueed IUGR on the development of myelination in rat brain.Fasting of pregnant dam for embryonic day 17-20 successfully gave rise to IUGR pups with 13% reduced mean body weight. In this model on P15, we found not-reduced but increased expressions of MBP and PLP in cerebellum and striatum compared with control group. Also, the expression of IGF-1 increased significantly even on P15.These results indicate that IUGR resulting from intra-uterine undernutrition induces the prenatal robust expression of IGF-1, which may promote the expressions of the myelin-associated genes (MBP and PLP) in rat cerebellum and striatum.