2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside Restores BDNF-TrkB and FGF2-Akt Signaling Axis to Attenuate Stress-induced Depression
2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside Restores BDNF-TrkB and FGF2-Akt Signaling Axis to Attenuate Stress-induced Depression
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2,3,5,4'-四羟基芪-2-O-β-D-葡萄糖苷恢复 BDNF-TrkB 和 FGF2-Akt 信号轴以减轻压力引起的抑郁症
DOI：
10.1016/j.neuroscience.2020.01.025
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发表时间：
2020-03-15
期刊：
影响因子：
3.3
通讯作者：
Qin, Xiao-Yan
中科院分区：
文献类型：
--
作者：
Li, Xi-Xi;Yu, Yun;Qin, Xiao-Yan
抑郁是一种长期的抑制性情绪，严重影响人类的健康。我们先前已经证明了2，3，5，4 '-四羟基二苯乙烯-2-O-β-D-葡萄糖苷（THSG）通过恢复氧化途径和神经炎症在慢性束缚应激（CRS）诱导的抑郁样小鼠中的抗抑郁作用。在这项研究中，我们研究了CRS诱导的抑郁样小鼠中神经营养因子的状况，以及THSG是否可以通过改善神经营养因子及其相关信号轴而成为抗抑郁剂。CRS导致海马和前额叶皮质抗氧化剂水平下调，脑源性神经营养因子（BDNF）、成纤维细胞生长因子2（FGF 2）及相关信号调节因子水平下降，表现为行为失能和快感缺乏。THSG的施用恢复了抗氧化剂和神经营养因子BDNF、FGF 2的表达。此外，THSG还能恢复Akt信号通路，拮抗Bcl-2和cleaved-caspase-3的表达，抑制细胞凋亡。同时，行为表现从CRS引起的运动能力丧失和快感缺乏中恢复。总之，THSG通过改善神经营养因子及其相关信号通路的生物化学而有效减轻应激诱导的抑郁症。这些结果为以BDNF为靶点开发民间抗抑郁药物提供了一条途径。(C)2020年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Depression is a long term inhibitory mood that heavily disabled human beings. We have previously demonstrated anti-depression effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) in chronic-restraint stress (CRS) induced depressive-like mice by restoring the oxidative pathway and neuroinflammation. In this study, we examine the conditions of neurotrophins in CRS-induced depressive-like mice and whether THSG could be an antidepressant by ameliorating the neurotrophins and their associated signaling axis. CRS produced downregulation of antioxidants, the decline of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and associated signaling regulators in the hippocampus and prefrontal cortex, corresponding to the behavioral inability and anhedonia. Administration of THSG restored the expression of antioxidants and neurotrophins BDNF, FGF2. Besides, THSG recovered the Akt signaling pathway and antagonistically restored the expression of Bcl-2 and cleaved-caspase-3 to inhibit apoptosis. Consistently, behavioral performances were recovered from CRS-induced motor inability and anhedonia. In summary, THSG is effective to attenuate stress-induced depression by ameliorating the biochemistry of neurotrophins and their related signaling pathways. These results may provide an avenue to take BDNF as a target to explore folk medicine for anti depression. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.