Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.
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DOI：
10.1016/j.cmet.2013.09.008
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发表时间：
2013-11-05
期刊：
影响因子：
29
通讯作者：
Spiegelman BM
中科院分区：
文献类型：
--
作者：
Wrann CD;White JP;Salogiannnis J;Laznik-Bogoslavski D;Wu J;Ma D;Lin JD;Greenberg ME;Spiegelman BM
运动可以改善认知功能，并与脑源性神经营养因子（BDNF）的表达增加有关。然而，驱动这种神经营养因子升高的潜在分子机制尚不清楚。在这里，我们发现FNDC5，一种先前发现的肌肉蛋白，在运动中被诱导，被切割并以鸢尾素的形式分泌，也通过耐力运动在小鼠海马中升高。神经元Fndc5基因表达受PGC-1α调控，Pgc1a−/−小鼠脑内Fndc5表达降低。原代皮质神经元中FNDC5的强制表达增加了Bdnf的表达，而rnai介导的FNDC5的敲低则降低了Bdnf的表达。重要的是，通过腺病毒载体将FNDC5外周递送到肝脏，导致血中鸢尾素升高，诱导海马中Bdnf和其他神经保护基因的表达。综上所述，我们的研究结果将耐力运动和重要的代谢介质PGC-1α和FNDC5与大脑中BDNF的表达联系起来。
Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α and Pgc1a−/− mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain.
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