Prophylactic treatment of curcumin in a rat model of depression by attenuating hippocampal synaptic loss
Prophylactic treatment of curcumin in a rat model of depression by attenuating hippocampal synaptic loss
复制标题
通过减轻海马突触损失来预防性治疗抑郁症大鼠模型中的姜黄素。
DOI：
10.1039/d1fo02676c
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发表时间：
2021-10-06
期刊：
影响因子：
6.1
通讯作者：
Yu, Shu Yan
中科院分区：
文献类型：
--
作者：
Fan, Cuiqin;Li, Ye;Yu, Shu Yan
姜黄素是一种多酚物质，被认为可有效治疗多种神经退行性疾病。然而，有关姜黄素对抑郁症等神经精神疾病的保护作用的确切机制的细节仍然未知。在重度抑郁症（MDD）的发病机制中，氧化应激和免疫系统（尤其是海马区）的失调可能发挥着关键作用。在此，我们表明，姜黄素（40 mg kg-1）预处理可减轻 LPS 诱导的抑郁症大鼠模型中的抑郁样行为，并伴有抑制氧化应激和炎症以及抑制海马 CA1 区神经元凋亡的作用，超微结构电生理实验结果表明，姜黄素 在这种 LPS 诱导的大鼠模型中，预处理显着防止了过度的突触损失并增强了突触功能。此外，姜黄素减弱了 miR-146a-5p 水平的增加和 p-ERK 信号表达的减少，这些信号通常发生在这些抑郁大鼠的 CA1 区域内。综上所述，这些结果表明姜黄素通过抑制氧化应激、神经炎症及其对突触失调的相关影响来发挥神经保护和抗抑郁活性。姜黄素产生这些有益作用的机制之一似乎涉及海马 CA1 区域内的 miR-146a-5p/ERK 信号通路。这些发现不仅阐明了姜黄素神经保护/抗抑郁作用的一些机制，而且还表明姜黄素作为抑郁症潜在治疗策略的作用。
Curcumin is a polyphenol substance considered to be effective in the treatment of a number of neurodegenerative diseases. However, details regarding the exact mechanisms for the protective effects of curcumin in neuropsychiatric disorders, like depression, remain unknown. In the pathogenesis of major depressive disorder (MDD) it appears that dysregulation of oxidative stress and immune systems, particularly within the hippocampal region, may play a critical role. Here, we show that pre-treatment with curcumin (40 mg kg-1) alleviates depression-like behaviors in a LPS-induced rat model of depression, effects which were accompanied with suppression of oxidative stress and inflammation and an inhibition of neuronal apoptosis in the hippocampal CA1 region, and results from ultramicrostructure electrophysiological experiments revealed that the curcumin pre-treatment significantly prevented excessive synaptic loss and enhanced synaptic functioning in this LPS-induced rat model. In addition, curcumin attenuated the increases in levels of miR-146a-5p and decreases in the expression of p-ERK signaling that would normally occur within CA1 regions of these depressed rats. Taken together, these results demonstrated that curcumin exerts neuroprotective and antidepressant activities by suppressing oxidative stress, neural inflammation and their related effects upon synaptic dysregulation. One of the mechanisms for these beneficial effects of curcumin appears to involve the miR-146a-5p/ERK signaling pathway within the hippocampal CA1 region. These findings not only elucidated some of the mechanisms underlying the neuroprotective/antidepressant effects of curcumin, but also suggested a role of curcumin as a potential therapeutic strategy for depression.