THE INSULIN-LIKE GROWTH-FACTOR-I SYSTEM IN THE RAT CEREBELLUM - DEVELOPMENTAL REGULATION AND ROLE IN NEURONAL SURVIVAL AND DIFFERENTIATION

The developmental regulation of insulin-like growth factor I(IGF-I), i ts receptor, and its binding proteins (IGFBPs) was studied in the rat cerebellum. All the components of the IGF-I system were detectable in the cerebellum at least by embryonic day 19. Levels of IGF-I receptor and its mRNA were highest at perinatal ages and steadily decrease ther eafter, although a partial recovery in IGF-I receptor mRNA was found i n adults. Levels of IGF-I and its mRNA also peaked at early ages, alth ough immunoreactive IGF-I showed a second peak during adulthood. Final ly, levels of IGFBPs were also highest at early postnatal ages and abr uptly decreased thereafter to reach lower adult levels. Since highest levels of the different components of the IGF-I system were found at p eriods of active cellular growth and differentiation we also examined possible trophic effects of IGF-I on developing cerebellar cells in vi tro. We found a dose-dependent effect of IGF-I on neuron survival toge ther with a specific increase of the two main neurotransmitters used b y cerebellar neurons, GABA and glutamate. Analysis of cerebellar cultu res by combined in vitro autoradiography and immunocytochemistry with cell-specific markers indicated that both Purkinje cells (calbindin-po sitive) and other neurons (neurofilament-positive) contain IGF-I bindi ng sites. These results extend previous observations on a developmenta l regulation of the IGF-I system in the cerebellum and reinforce the n otion of a physiologically relevant trophic role of IGF-I in cerebella r development. (C) 1994 Wiley-Liss, Inc.