A New Perspective on Ameliorating Depression-Like Behaviors: Suppressing Neuroinflammation by Upregulating PGC-1α
A New Perspective on Ameliorating Depression-Like Behaviors: Suppressing Neuroinflammation by Upregulating PGC-1α
复制标题
改善抑郁样行为的新视角：通过上调 PGC-1α 抑制神经炎症
DOI：
10.1007/s12640-020-00292-z
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发表时间：
2020-10-06
影响因子：
3.7
通讯作者：
Ma, Zhanqiang
中科院分区：
文献类型：
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作者：
Fu, Xinxin;Jiao, Jie;Ma, Zhanqiang
炎症在抑郁症病理学中起着重要作用，使其成为改善抑郁样行为的有希望的靶点。过氧化物酶体增殖物激活受体γ共激活因子-1 α（PGC-1 α）是一种转录共激活因子，能够通过NF-κ B信号传导抑制炎症事件。然而，PGC-1 α在抑郁症中的作用尚不清楚。本研究旨在探讨PGC-1 α在抑郁症中的作用及其机制。用慢性不可预测的轻度刺激（CIMIS）建立小鼠模型，探讨抑郁样行为与PGC-1 α之间的关系。黄芩苷用于评价调节PGC-1 α的作用。在BV2-SH-SY5Y共培养体系和LPS刺激的小鼠模型中观察黄芩苷的抗炎作用。在靶向NF-κ B信号传导的基因沉默条件下，在细胞共培养系统中探索PGC-1 α在神经炎症中的作用。结果发现，LPS和LPS均可抑制小鼠海马PGC-1 α的表达，黄芩苷可增加PGC-1 α的表达，减轻抑郁样行为。黄芩苷通过调节NF-κ B信号通路减轻LPS刺激小鼠海马和BV2-SH-SY5 Y共培养系统的神经炎症反应;而PGC-1 α的敲除可逆转黄芩苷对神经炎症反应和NF-κ B信号通路的影响。我们的研究结果揭示了PGC-1 α在减轻抑郁症神经炎症中的重要作用，表明PGC-1 α可能是抑郁症的治疗靶点。
Inflammation plays an important role in depression pathology, making it a promising target for ameliorating depression-like behaviors. The peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a transcriptional coactivator being able to constrain inflammatory events through NF-kappa B signaling. However, the role of PGC-1 alpha in depression is not yet clear. This study was designed to investigate the role of PGC-1 alpha in depression and explore the underlying mechanisms. Mice modeled with chronic unpredictable mild stimulation (CUMS) were explored for the relationship between depression-like behaviors and PGC-1 alpha. Baicalin was used to evaluate the effect regulating PGC-1 alpha. Furthermore, the anti-neuroinflammatory effect of baicalin was investigated both in BV2-SH-SY5Y co-culture system and in mice by LPS challenge. The role of PGC-1 alpha in neuroinflammation was explored in cell co-culture systems under gene silencing conditions targeting NF-kappa B signaling. We found that the expression of PGC-1 alpha was inhibited in the hippocampus of mice exposed to CUMS or LPS, while baicalin could increase the expression of PGC-1 alpha and alleviate the depression-like behaviors. Furthermore, baicalin attenuated neuroinflammation in the hippocampus of mice and BV2-SH-SY5Y co-culture system by LPS challenge via regulating NF-kappa B signaling; however, knockdown of the PGC-1 alpha could reverse the effect of baicalin on neuroinflammation and NF-kappa B signaling. Our results revealed a vital role for PGC-1 alpha in attenuating neuroinflammation in depression, indicating that PGC-1 alpha might be a therapeutic target for depression.