Interleukin-6: Its role and mechanisms in rescuing depression-like behaviors in rat models of depression
Interleukin-6: Its role and mechanisms in rescuing depression-like behaviors in rat models of depression
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Interleukin-6：其在拯救抑郁症大鼠模型抑郁样行为中的作用和机制
DOI：
10.1016/j.bbi.2019.08.002
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发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
Shu Yan Yu
中科院分区：
文献类型：
--
作者：
Peng Wang;Yabo Feng;Liyan Wang;Ye Li;Cuiqin Fan;Qiqi Song;Shu Yan Yu
特定脑区的神经元损伤被认为是抑郁症病理生理学中的一个关键危险因素。然而，这一过程的潜在机制，以及因此在抑郁症治疗中开发新的治疗策略的潜力，在很大程度上仍然未知。在这里，我们报告说，IL-6保护与抑郁症相关的神经元异常，部分，通过抑制氧化应激和随之而来的自噬和凋亡过度活跃。具体来说，我们表明，IL-6下调CA 1海马在两个动物模型的抑郁症和上调抗抑郁药。CA 1区IL-6水平的增加导致多效性保护作用，包括减少氧化应激和调节CA 1神经元中的自噬、抗免疫炎症激活和抗凋亡作用，所有这些都与抑郁样行为的拯救相关。相反，IL-6下调加剧了CA 1区域内的神经元异常，并促进大鼠抑郁症表型的发生。有趣的是，除了减轻氧化损伤外，抗氧化剂N-乙酰半胱氨酸（NAC）还与大鼠神经元缺陷的显着减少和抑郁行为的表现有关。这些结果表明，IL-6可能发挥神经保护作用的CA 1神经元通过多效性机制，并可能作为一个潜在的治疗抑郁症的治疗靶点。
Neuronal injury within specific brain regions is considered a critical risk factor in the pathophysiology of depression. However, the underlying mechanisms of this process, and thus the potential for development of novel therapeutic strategies in the treatment of depression, remain largely unknown. Here, we report that Il-6 protects against neuronal anomalies related with depression, in part, by suppressing oxidative stress and consequent autophagic and apoptotic hyperactivity. Specifically, we show that IL-6 is downregulated within the CA1 hippocampus in two animal models of depression and upregulated by antidepressants. Increasing levels of IL-6 in the CA1 region result in pleiotropic protective actions including reductions in oxidative stress and modulation of autophagy, anti-immuno-inflammatory activation and anti-apoptotic effects in CA1 neurons, all of which are associated with the rescue of depression-like behaviors. In contrast, IL-6 downregulation exacerbates neuronal anomalies within the CA1 region and facilitates the genesis of depression phenotypes in rats. Interestingly, in addition to attenuating oxidative damage, the antioxidant, N-acetylcysteine (NAC), is also associated with significantly decreased neuronal deficits and the display of depressive behaviors in rats. These results suggest that IL-6 may exert neuroprotection within CA1 neurons via pleiotropic mechanisms and may serve as a potential therapeutic target for the treatment of depression.
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创伤后，通过上调白介素（IL）6和IL-6受体的表达来加速小鼠的神经再生。
影响因子：
15.3
作者：
Hirota, H;Kiyama, H;Kishimoto, T;Taga, T
通讯作者：
Taga, T
DOI：
10.1016/j.bbi.2015.06.001
发表时间：
2015-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Haapakoski R;Mathieu J;Ebmeier KP;Alenius H;Kivimäki M
通讯作者：
Kivimäki M
影响因子：
7.4
作者：
Levonen, Anna-Liisa;Hill, Bradford G.;Kansanen, Emilia;Zhang, Jianhua;Darley-Usmar, Victor M.
通讯作者：
Darley-Usmar, Victor M.
影响因子：
4.3
作者：
Colpo GD;Leboyer M;Dantzer R;Trivedi MH;Teixeira AL
通讯作者：
Teixeira AL
影响因子：
9.2
作者：
Erta M;Quintana A;Hidalgo J
通讯作者：
Hidalgo J