Zhang W, Ghetti B, Lee W H
Herman B. Wells Center for Pediatric Research, Department of Anatomy, Indiana University School of Medicine, Indianapolis 46202, USA.
Brain Res Dev Brain Res. 1997 Feb 20;98(2):164-76. doi: 10.1016/s0165-3806(96)00168-x.
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 is the cause or result of the Purkinje cell degeneration needs to be further elucidated.
胰岛素样生长因子I（IGF-I）在大鼠小脑发育中发挥潜在功能作用，这在出生后关键生长期其与胰岛素样生长因子I受体（IGFR-I）、胰岛素样生长因子结合蛋白（IGFBP）2和5的时空协调表达中得到体现。尽管IGF-I可促进培养的小脑神经元存活，但其在体内小脑发育过程中的作用尚不清楚。生长因子剥夺已被证明会引发凋亡，即发育性细胞死亡，若异常则可能导致各种病理状态。为了解IGF-I在浦肯野细胞存活中的作用，我们检测了浦肯野细胞变性（pcd）小鼠中IGF-I、IGFR-I、IGFBP 2和5的mRNA表达。在pcd小脑发育过程中，浦肯野细胞迅速退化，到成年时几乎完全耗尽。在出生后第（D）11、17、24天及成年期，研究了pcd突变体（pcd/pcd）浦肯野细胞死亡期间IGF系统mRNA表达。在D11和D十七，正常小脑和pcd/pcd小脑之间未观察到IGF-I系统mRNA表达的显著差异。在D24，pcd/pcd小脑中凋亡的浦肯野细胞中IGF-I mRNA显著减少，同时伴有严重的星形胶质细胞增生和星形胶质细胞IGF-I表达的激活。在成年pcd/pcd小脑中，由于剩余的浦肯野细胞很少，许多颗粒细胞发生凋亡。总之，IGF-I mRNA表达降低与pcd小脑中浦肯野细胞凋亡相关。IGF-I mRNA表达降低是浦肯野细胞变性的原因还是结果，有待进一步阐明。
