Metabolic factors-triggered inflammatory response drives anti-depressant effects of exercise in CUMS rats
Metabolic factors-triggered inflammatory response drives anti-depressant effects of exercise in CUMS rats
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代谢因素引发的炎症反应驱动 CUMS 大鼠运动的抗抑郁作用
DOI：
10.1016/j.psychres.2015.05.102
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发表时间：
2015-08-30
影响因子：
11.3
通讯作者：
Ji, Liu
中科院分区：
文献类型：
--
作者：
Liu, Weina;Wang, Hongmei;Ji, Liu
慢性应激是抑郁症的一个潜在因素，伴随着代谢和炎症反应。运动被认为是治疗抑郁症的一种方法，但其有益作用的机制仍然未知。本研究的目的是证实代谢因子触发的炎症反应介导的慢性不可预测的轻度应激（CIMTS）大鼠运动的抗抑郁作用。已经发现，BRAS刺激ghrelin及其受体Ghsr的表达，但抑制瘦素及其受体LepRb的表达。Ghrelin通过与Ghsr结合，诱导GSK-3 β在Tyr 216上的磷酸化，并降低在Ser 9上的磷酸化，从而增加GSK-3 β活性。相反，ghrelin结合Ghsr降低STAT 3的活性，通过减少磷酸化的STAT 3的Tyr 705和增加Ser 727磷酸化。与生长素释放肽呈负相关，瘦素与LepRb的结合通过磷酸化对GSK-3 β和STAT 3的活性产生相反的影响。此外，降低的瘦素水平通过LepRb启动NLRP 3活性。此外，GSK-3 β抑制STAT 3活化，从而促进NLRP 3的表达。同时，游泳改善代谢和炎症反应，无论是在SAMS和对照组大鼠。我们的研究结果表明，运动不仅可以改善抑郁症的代谢紊乱和炎症反应，而且还有助于正常情况下的代谢和炎症功能。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Chronic stress is a potential contributing factor for depression, accompanying with metabolic and inflammatory response. Exercise is considered as a treatment for depression, but mechanisms underlying its beneficial effects still remain unknown. The objectives of present study were to confirm that metabolic factors-triggered inflammatory response mediates the antidepressant actions of exercise in chronic unpredictable mild stress (CUMS) rats. It has been found that CUMS stimulated expression of ghrelin and its receptor Ghsr, but inhibited expression of leptin and its receptor LepRb. Ghrelin, via binding to Ghsr, induced phosphorylation of GSK-3 beta on Tyr216 and decreased phosphorylation on Ser9, thus increasing GSK-3 beta activity. Conversely, ghrelin binding to Ghsr decreased STAT3 activity, through decreasing phosphorylation of STAT3 on Tyr705 and increasing Ser727 phosphorylation. Negatively correlated with ghrelin, leptin binding to LepRb had opposite effects on the activity of GSK-3 beta and STAT3 via phosphorylation. In addition, decreased leptin level initiated NLRP3 activity via LepRb. Furthermore, GSK-3 beta inhibited STAT3 activation, thus promoting the expression of NLRP3. Meanwhile, swim improved metabolic and inflammatory response both in CUMS and control rats. Our findings suggest that exercise not only ameliorates metabolic disturbance and inflammatory response in depression, but also contributes to metabolic and inflammatory function in normal conditions. (C) 2015 Elsevier Ireland Ltd. All rights reserved.