Insulin-Like Growth Factor-I Overexpression Attenuates Cerebellar Apoptosis by Altering the Expression of Bcl Family Proteins in a Developmentally Specific Manner

In studies of transgenic (Tg) mice that overexpress insulin-like growth factor-I (IGF-I) exclusively in the CNS, we demonstrated a dramatic increase in cerebellar granule cell number that appeared to be attributable predominantly to enhanced survival. IGF-I anti-apoptotic actions are well established in cultured neurons, but comparable studies in vivo are few. Using the same Tg mice, therefore, we set out to document IGF-I antiapoptotic effects during cerebellar development and to probe IGF-I signaling mechanisms. Compared with cerebella (CBs) of non-Tg littermates, those of Tg mice had fewer apoptotic cells at postnatal day 7 (P7) and showed a similar tendency at P14 and P21. At each age studied, procaspase-3 and caspase-3 were decreased in CBs of Tg mice. The caspase-3 decline was accompanied by decreases in the 85 kDa fragment of Poly(ADP-ribose) polymerase, a known product of caspas