Decreased IGF-I gene expression during the apoptosis of Purkinje cells in pcd mice

Abstract

Insulin-like growth factor I (IGF-I) plays a potential functional role in cerebellar development in the rat, as indicated by its spatio-temporally coordinated expression with the IGF-I receptor (IGFR-I), IGF binding protein (IGFBP) 2 and 5 during the postnatal critical growth period. Although IGF-I promotes the survival of cultured cerebellar neurons, its role during cerebellar development in vivo is unclear. Growth factor deprivation has been shown to trigger apoptosis, the developmental cell death which, if abnormal, may lead to various pathological states. To understand the involvement of IGF-I in Purkinje cell survival, we examined mRNA expression of IGF-I, IGFR-I, IGFBP 2 and 5 in the Purkinje cell degeneration ( pcd) mice. During pcd cerebellar development, Purkinje cells rapidly degenerate leading to their almost complete depletion by adult life. IGF system mRNA expression was studied during Purkinje cell death in the pcd mutants ( pcd pcd ) at postnatal day (D) 11, 17, 24 and adult. At D11 and D17, no significant difference of the IGF-I system mRNA expression was observed between the normal and pcd pcd cerebellum. At D24, a significant decrease of IGF-I mRNA was found in the apoptotic Purkinje cells in the pcd pcd cerebellum, which was accompanied by a severe astrogliosis and activation of astrocytic IGF-I expression. In the adult pcd pcd cerebellum, with few Purkinje cells remaining, many granule cells underwent apoptosis. In conclusion, decreased IGF-I mRNA expression was correlated with Purkinje cell apoptosis in pcd cerebellum. Whether the decrease of IGF-I mRNA expression in the cause or result of the Purkinje cell degeneration needs to be further elucidated.