PGC-1α–FNDC5–BDNF signaling pathway in skeletal muscle confers resilience to stress in mice subjected to chronic social defeat
PGC-1α–FNDC5–BDNF signaling pathway in skeletal muscle confers resilience to stress in mice subjected to chronic social defeat
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骨骼肌中的 PGC-1α→FNDC5→BDNF 信号通路赋予遭受慢性社交失败的小鼠压力恢复能力
DOI：
10.1007/s00213-018-5041-2
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发表时间：
2018
影响因子：
3.4
通讯作者：
Chun Yang
中科院分区：
文献类型：
--
作者：
Gaofeng Zhan;Niannian Huang;Shan Li;Dongyu Hua;Jie Zhang;Xi Fang;Ning Yang;Ailin Luo;Chun Yang
骨骼肌消耗身体三分之二的能量，可能在与压力有关的疾病中发挥作用。有证据表明，骨骼肌中的过氧化物酶体增殖物激活受体γ共激活因子α（PGC-1 α）-纤连蛋白III型含结构域5（FNDC5）-脑源性神经营养因子（BDNF）信号通路在赋予运动的有益效果中起关键作用。在这项研究中，我们的目的是确定这一途径是否有助于遭受慢性社会失败压力（CSDS）的小鼠的恢复力或易感性。与对照组相比，敏感但不恢复的小鼠内侧前额叶皮层和丘脑核中的BDNF-原肌球蛋白受体激酶B（Trk B）和proBDNF-p75 NTR信号发生了显著改变。此外，易感小鼠骨骼肌中PGC-1 α、FNDC5和BDNF的水平以及p-TrkB/TrkB比值均显著低于对照组，而易感小鼠骨骼肌中proBDNF和p75NTR的水平显著高于对照组。此外，社会互动测试数据与骨骼肌中PGC-1 α、FNDC5和BDNF的表达或p-TrkB/TrkB比值之间存在显著正相关。这些结果表明，骨骼肌中PGC-1 α-FNDC5-BDNF信号通路的下调有助于恢复力与对CSDS的易感性。因此，骨骼肌中这一通路的改变可能在介导应激相关疾病中起着至关重要的作用。
Skeletal muscle consumes two thirds of the body’s energy and may play a role in stress-related disorders. Evidence suggests that the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α)–fibronectin type III domain-containing 5 (FNDC5)–brain-derived neurotrophic factor (BDNF) signaling pathway in skeletal muscle plays a key role in conferring the beneficial effects of exercise. In this study, we aimed to determine whether this pathway contributes to the resilience or susceptibility of mice subjected to chronic social defeat stress (CSDS). BDNF–tropomyosin receptor kinase B (TrkB) and proBDNF–p75NTRsignaling in the medial prefrontal cortex and nucleus accumbens of susceptible but not resilient mice were significantly altered compared with the controls. Furthermore, the levels of PGC-1α, FNDC5, and BDNF, as well as the p-TrkB/TrkB ratio in the skeletal muscle of susceptible but not resilient mice, were significantly lower than those of the controls, but the levels of proBDNF and p75NTRin the skeletal muscle of susceptible mice were significantly higher than those of the controls. Moreover, there were significant positive associations between social interaction test data and the expression of PGC-1α, FNDC5, and BDNF or the p-TrkB/TrkB ratio in skeletal muscle. These results suggest that the downregulation of the PGC-1α–FNDC5–BDNF signaling pathway in skeletal muscle contributes to resilience vs. susceptibility to CSDS. Therefore, alterations in this pathway in skeletal muscle may play a crucial role in mediating stress-related disorders.