Center for Translational Systems Biology and Neuroscience, School of Basic Biomedical Science, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Eur J Pharmacol. 2018 Aug 15;833:1-7. doi: 10.1016/j.ejphar.2018.05.020. Epub 2018 May 18.
The purpose of the present study was to investigate whether ɑ-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 ɑ-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 ɑ-tocopherol, as well as its three downstream pathways. Taken together, our study found that ɑ-tocopherol might potentially promote autophagy to induce anti-depressive responses in CUMS mice though the AMPK/mTOR pathway.
本研究旨在探讨 α-生育酚是否通过调节自噬来发挥其在慢性不可预测轻度应激（CUMS）小鼠中的神经保护作用。α-生育酚给药后，改善了行为测试（包括蔗糖偏好测试、旷场测试、强迫游泳测试和悬尾测试）中的缺陷。为了研究潜在的机制，对前额叶皮层和海马样本进行了 Western blot 分析。与自噬程度相似，在 CUMS 刺激后，腺苷单磷酸激活蛋白激酶（AMPK）和 Unc-51 样自噬激活激酶-1（ULK1）的活性降低。此外，我们还发现哺乳动物雷帕霉素靶蛋白（mTOR）的活性增加，而α-生育酚给药后其三个下游途径也受到显著影响。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 CUMS 小鼠产生抗抑郁反应。
