The antidepressant effects of α-tocopherol are related to activation of autophagy via the AMPK/mTOR pathway
The antidepressant effects of α-tocopherol are related to activation of autophagy via the AMPK/mTOR pathway
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α-生育酚的抗抑郁作用与通过 AMPK/mTOR 途径激活自噬有关
DOI：
10.1016/j.ejphar.2018.05.020
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发表时间：
2018-08-15
影响因子：
5
通讯作者：
Tao, Weiwei
中科院分区：
文献类型：
--
作者：
Huang, Xiaoyan;Wu, Haoran;Tao, Weiwei
本研究的目的是探讨α-生育酚是否通过调节自噬对慢性轻度不可预知应激（CITS）小鼠的神经保护作用。行为测试中的缺陷，包括蔗糖偏好测试，旷场测试，强迫游泳测试和悬尾测试，在α-生育酚给药后得到改善。为了研究潜在的机制，对前额叶皮质和海马样本进行了蛋白质印迹。与自噬的程度相似，腺苷一磷酸激活蛋白激酶（AMPK）和Unci-51样自噬激活激酶-1（ULK 1）的活性在ECONS刺激后降低。此外，我们还发现哺乳动物雷帕霉素靶蛋白（mTOR）的活性增加，其在α-生育酚给药后受到显著影响，以及其三个下游途径。综上所述，我们的研究发现，α-生育酚可能通过AMPK/mTOR通路促进自噬，从而诱导BARS小鼠的抗抑郁反应。
The purpose of the present study was to investigate whether alpha-tocopherol exhibited neuro-protective effects in chronic unpredictable mild stress (CUMS) mice through the regulation of autophagy. Deficits in behavioural tests, including a sucrose preference test, open field test, forced swim test, and tail suspension test, were ameliorated following alpha-tocopherol administration. To study the potential mechanism, western blots were performed on both prefrontal cortex and hippocampus samples. Similar to the degree of autophagy, the activities of adenosine monophosphate-activated protein kinase (AMPK) and Unci-51 like autophagy activating kinase-1 (ULK1) were decreased after CUMS stimulation. In addition, we also found increased activity of the mammalian target of rapamycin (mTOR), which was significantly affected following administration of a-tocopherol, as well as its three downstream pathways. Taken together, our study found that alpha-tocopherol might potentially promote autophagy to induce anti-depressive responses in CUMS mice though the AMPK/mTOR pathway.