神经递质、神经营养因子对海马干细胞分化影响的研究

Effects of Neurotrophic Factors and Neurotransmitters on Differentiation of Hippocampal Stem Cells

目的探讨脑源性神经营养因子(BDNF)、胶质源性神经营养因子(GDNF)、谷氨酸及γ-氨基丁酸(GABA)对大鼠海马干细胞分化的影响。方法对大鼠海马干细胞进行体外培养,培养液中加入不同剂量的BDNF、GDNF、谷氨酸及GABA,应用免疫荧光方法观察,并计算微管相关蛋白(MAP-2ab)及胶质纤维酸性蛋白(GFAP)阳性细胞率。结果在神经干细胞分化的第7、14天,与对照组比,BDNF、GDNF、谷氨酸及GABA剂量依赖性地增加表达MAP-2ab阳性细胞率(P<0.05);而对GFAP表达主要是抑制性的,且随分化时间及BDNF、GDNF、谷氨酸及GABA的浓度不同而不同。结论BDNF、GDNF、谷氨酸和GABA均可明显促进神经干细胞分化为神经元,且GDNF的作用大于BDNF。谷氨酸和GABA作用最佳浓度可能需随分化时间的不同而进行调整。

Objective To investigate the effects of brain cell line-derived neurotrophic factor （BDNF）, glial cell line-derived neurotrophic factor （GDNF） and neurotransmitters including glutaimic acid （GA） and gamma-aminobutyric acid （GABA） on the differentiation of hippocampal stem cells derived from rats. Methods The hippocampal stem cells derived from the rats were in vitro cultured respectively in the media containing different doses of BDNF, GDNF, GA and GABA. The expressions of microtubuleassociated protein-2ab（MAP-2ab） and glial fibrillary acidic protein （GFAP） were determined by immunocytochemical technique. The rates of MAP-2ab and GFAP positive cells were calculated. Results BDNF, GDNF, GA and GABA produced significantly concentration-dependent increase in MAP-2ab-positive cells rate 7 and 14 clays after the differentiation of bippocampal stem cells compared to the control group （P〈0.05）. The effects of BDNF, GDNF, GA and GABA on GFAP expression were mainly inhibitory and were different with the time of differentiation of the hippocampal stem cells and their different concentration. Conclusion BDNF, GDNF, GA and GABA can promote hippocampal stem cells differentiation into neurons in rats, and the effect of GDNF was stronger than that of BDNF.