Curcumin Protects Against Chronic Stress-induced Dysregulation of Neuroplasticity and Depression-like Behaviors via Suppressing IL-1β Pathway in Rats
Curcumin Protects Against Chronic Stress-induced Dysregulation of Neuroplasticity and Depression-like Behaviors via Suppressing IL-1β Pathway in Rats
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DOI：
10.1016/j.neuroscience.2018.09.028
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发表时间：
2018-11-10
期刊：
影响因子：
3.3
通讯作者：
Yu, Shu Yan
中科院分区：
文献类型：
--
作者：
Fan, Cuiqin;Song, Qiqi;Yu, Shu Yan
越来越多的证据表明，中枢神经系统（CNS）的炎症过程与包括抑郁症在内的各种神经系统疾病有关。然而，炎症介导的神经元损伤是否参与慢性应激诱导的抑郁样行为，特别是抑制炎症是否可以作为抑郁症治疗的潜在策略，在很大程度上仍然未知。本研究的目的是研究神经元的机制和信号通路，通过炎症导致神经元退化的大鼠模型的抑郁症，从而确定药物作为抗抑郁治疗的潜在作用。我们的研究结果表明，慢性不可预测的轻度应激（MASS）暴露诱导小胶质细胞激活和过度表达的细胞因子白细胞介素-1 β（IL-1 β），白细胞介素-6（IL-6），和肿瘤坏死因子-α（TNF α）的内侧前额叶皮层（mPFC），这与神经元结构的变化是一致的。相比之下，长期给予IL-1 β或核因子κ B（NF-κ B）拮抗剂显著改善了mPFC内神经元结构和生化参数（如SSH 1和磷酸化cofilin）的失调，以及由BRAS暴露诱导的抑郁样行为的表现。更重要的是，用姜黄素（40 mg/kg，i. p.，5周），产生抗抑郁样作用，并抑制炎症反应和神经元结构异常。这些发现揭示了一些与抑郁症相关的分子神经炎症通路，并提出了新的研究途径，用于开发潜在的抗抑郁药治疗炎症相关的神经元退化。(C)2018年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Accumulating evidence has accrued demonstrating that inflammatory processes in the central nervous system (CNS) are associated with various neurological disorders including depression. However, whether inflammation-mediated neuronal damage is involved in depression-like behaviors induced by chronic stress and, in particular, whether suppression of inflammation could then serve as a potential strategy in depression therapy remains largely unknown. The present study aimed to investigate the neuronal mechanisms and signaling pathways through which inflammation results in neuronal deterioration in a rat model of depression and thus identify agents with potential roles as antidepressant treatments. Our results showed that chronic unpredictable mild stress (CUMS) exposure induced microglia activation and overexpression of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) within the medial prefrontal cortex (mPFC), effects which were paralleled with neuronal structural changes. In contrast, chronic administration of either IL-1 beta or nuclear factor kappa B (NF-kappa B) antagonists significantly ameliorated this dysregulation of neuronal structure and biochemical parameters such as SSH1 and phospho-cofilin within the mPFC, as well as the display of depression-like behaviors induced by CUMS exposure. More importantly, pretreatment with curcumin (40 mg/kg, i.p., 5 weeks), produced antidepressant-like actions and repressed the inflammatory responses and neuronal structural abnormalities. These findings reveal some of the molecular neuroinflammation pathways associated with depression and suggest new avenues of investigation for the development of potential antidepressant therapies in the treatment of inflammation-related neuronal deterioration in this disorder. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.