关键词: 胰岛素样生长因子结合蛋白-4, 神经分化, 胰岛素样生长因子-Ⅰ型受体信号通路, 转基因小鼠

Abstract: Objective To explore the neuronal and glial differentiation in the brain of the insulin-like growth factor binding protein 4 (IGFBP4) transgenic mouse in which the gene was driven by a neuron-specific promoter platelet derived growth factor-β(PDGF-β). Methods The integrated expression cassette of PDGF-β promoter and IGFBP4 cDNA was identified using PCR and DNA sequencing. The proportion of oligodendrocyte precursors in the hippocampus was estimated via Isotropic Fractionator. Semi-quantitative analysis of neuronal and glial differentiation, IGF-IR pathway activation, and cell survival-related molecules in the hippocampus at postnatal day 28 was conducted by Western blotting. Animal behavior was assessed using Rotarod test. Results PDGF-β promoter and IGFBP4 cDNA were stably integrated in the transgenic mouse genome. The number of oligodendrocyte precursors and expression levels of myelin basic protein (MBP) in the hippocampus were significantly increased, neuronal and astrocytic markers NeuN and glial fibrillary acidic protein (GFAP) were not significantly changed in the brain of P28 transgenic mice. Phosphorylation levels of Erk1, 2 and Akt were significantly elevated while p38 activation remained unchangeable. Caspase-3 expression was significantly down-regulated, β-catenin and Bcl-2 levels were not changed. Animal movement on Rotarod was significantly improved, and NeuN expression in the cerebellum and cortex was significantly increased in the transgenic mouse at postnatal month 12. Conclusion Over-expression of IGFBP4 in neurons promoted oligodendrocytic and neuronal differentiation in the brain of the transgenic mice.

Key words: insulin-like growth factor binding protein 4, neural differentiation, insulin-like growth factor-Ⅰ receptor signal pathway, transgenic mouse