自主跑轮运动上调成年小鼠海马齿状回区细胞增殖及BDNF、IGF1和WNT4的表达水平

Voluntary wheel running enhances cell proliferation and expression levels of BDNF, IGF1 and WNT4 in dentate gyrus of adult mice

成年海马神经发生在调控学习记忆和情感过程中有重要作用。外界刺激因素,如自主运动能影响成年海马神经发生过程。自主运动能显著增强海马齿状回区的细胞增殖,并使新生神经元增多,但其具体机制仍不是十分清楚。本研究采用跑轮实验这种啮齿动物自主运动模型,使两月龄的C57BL/6成年小鼠跑轮15天后,用BrdU掺入实验观察海马齿状回区的细胞增殖情况。采用逆转录实时荧光定量PCR法(RT-qPCR)和蛋白免疫印迹法(Western blot)检测海马齿状回区、阿蒙角区和皮层区成年神经发生相关因子的mRNA和蛋白表达水平。结果显示,自主跑轮运动15天后的成年小鼠海马齿状回区增殖细胞数目显著上调;齿状回区Bdnf、Igf1的mRNA和蛋白表达水平显著升高,Wnt4的mRNA表达水平显著升高,提示15天自主运动可能通过特异地增加海马齿状回区BDNF、IGF1和WNT4的表达产生上调成年海马神经发生的作用。

Adult hippocampal neurogenesis plays important roles in learning, memory and mood regulation. External factors, such as physical exercise, have been found to modulate adult hippocampal neurogenesis. Voluntary running enhances cell proliferation in subgranular zone（SGZ） and increases the number of new born neurons in rodents, but underlying mechanisms are not fully understood. In this study, we used BrdU assay to identify proliferating cells in 2-month-old C57BL/6 mice after 15 days of voluntary wheel running test. mRNA and protein levels for several neural factors in dentate gyrus, Ammon＇s horn, and cortex were also analyzed by RT-qPCR and Western blot assay after 15 days of voluntary wheel running. Our data show that voluntary wheel running for 15 days elevated the number of proliferation cells in dentate gyrus and significantly up-regulated the mRNA levels of Bdnf, Igf1 and Wnt4. The protein levels of BDNF and IGF1 in dentate gyrus were also increased after voluntary wheel running. These results indicate that the increase of adult hippocampal neurogenesis caused by voluntary wheel running for 15 days might be through up-regulating BDNF, IGF1 and WNT4 in dentate gyrus.