Potential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge
Potential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge
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RagA-mTOR-p70S6K 轴与细菌脂糖挑战期间抑郁行为之间的潜在联系
DOI：
10.1186/s12974-019-1610-5
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发表时间：
2019-11
影响因子：
9.3
通讯作者：
Rong Jianhui
中科院分区：
文献类型：
--
作者：
Zhao Jia;Lao Lixing;Cui Wei;Rong Jianhui
背景细菌感染是抑郁症的一个潜在危险因素。然而，关于细菌内毒素和抑郁样行为之间的机制联系知之甚少。本研究旨在探讨脂多糖（liposaccharide，LPS）是否通过依次激活小G T β RagA、哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）和p70 S6 K诱导小鼠抑郁样行为。采用强迫游泳试验和悬尾试验评价动物的抑郁样行为。RagA，mTOR，和p70 S6 K的表达水平测定在小鼠，原代皮层神经元，神经干细胞，和PC 12 cells.ResultsLPS有效地诱导小鼠抑郁样行为。生化检测显示LPS不仅上调小鼠脑内RagA表达，而且激活mTOR/p70 S6 K通路。LPS刺激也在原代皮层神经元、神经干细胞和PC 12细胞中达到了类似的效果。用特异性siRNA沉默RagA表达后，LPS不能诱导mTORC 1易位到PC 12细胞的溶酶体膜。结论LPS可能通过上调RagA，激活mTOR/p70 S6 K通路诱导小鼠抑郁样行为。这样的信息可以突出RagA-mTOR-p70 S6 K信号级联作为开发新的抗肿瘤治疗剂的新的治疗靶点。
BackgroundBacterial infection is a potential risk factor for depression. However, little is known about the mechanistic link between bacterial endotoxin and depressive-like behaviors. The aim of the present study was to clarify whether liposaccharide (LPS) could induce depressive-like behaviors in mice via sequentially activating small GTPase RagA, mammalian target of rapamycin (mTOR), and p70S6K.MethodsC57BL/6 N mice were treated with 0.83 mg/kg LPS by intraperitoneal injection for 24 h. The animals were assessed for depressive-like behaviors by forced swim test and tail suspension test. The expression levels of RagA, mTOR, and p70S6K were determined in mice, primary cortical neurons, neural stem cells, and PC12 cells.ResultsLPS effectively induced depressive-like behaviors in mice. Biochemical examination revealed that LPS not only upregulated RagA expression but also activated mTOR/p70S6K pathway in mouse brains. LPS challenge also achieved a similar effect in primary cortical neurons, neural stem cells, and PC12 cells. Following the silencing of RagA expression with specific siRNA, LPS failed to induce mTORC1 translocation to the lysosomal membranes in PC12 cells. These results suggested that LPS might sequentially upregulate RagA and activate mTOR and p70S6K pathways in mice and neural stem cells.ConclusionsThis study for the first time demonstrated that LPS might induce depressive-like behaviors in mice via the upregulation of RagA and subsequent activation of mTOR/p70S6K pathway. Such information may highlight the RagA-mTOR-p70S6K signaling cascade as a novel therapeutic target for the development of new anti-depressant therapeutics.
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影响因子：
3.3
作者：
Wei Zhu;Jie Li;Yigang Liu;Kun Xie;Le Wang;Jianmin Fang
通讯作者：
Wei Zhu;Jie Li;Yigang Liu;Kun Xie;Le Wang;Jianmin Fang
LPS 和 UCMS 诱导的抑郁小鼠模型的行为、炎症和神经化学紊乱
DOI：
10.1016/j.bbr.2017.05.064
发表时间：
2017-05
期刊：
Behav Brain Res
影响因子：
--
作者：
Xinnan Zhao;Fengrui Cao;Qing Liu;Xinsheng Li;Guoyang Xu;Gang Liu;Yanli Zhang;Xiaohan Yang;Shansong Yi;Fenghua Xu;Kai Fan;Jianmei Ma
通讯作者：
Jianmei Ma
影响因子：
5.3
作者：
通讯作者：
--
DOI：
10.1177/0269881117711708
发表时间：
2017-09
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Kopschina Feltes P;Doorduin J;Klein HC;Juárez-Orozco LE;Dierckx RA;Moriguchi-Jeckel CM;de Vries EF
通讯作者：
de Vries EF
慢病毒介导的海马白介素 1 β (IL-1 β) 敲低可减轻脂多糖 (LPS) 诱导的小鼠记忆缺陷以及焦虑和抑郁样行为
影响因子：
9.3
作者：
Li M;Li C;Yu H;Cai X;Shen X;Sun X;Wang J;Zhang Y;Wang C
通讯作者：
Wang C