Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse
Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat Stress Induced Depression Mouse
复制标题
慢性社交挫败压力诱发抑郁症小鼠的小胶质细胞极化和内质网应激
DOI：
10.1007/s11064-018-2504-0
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发表时间：
2018-05-01
影响因子：
4.4
通讯作者：
Xiao, Baoguo
中科院分区：
文献类型：
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作者：
Tang, Jie;Yu, Wenbo;Xiao, Baoguo
近年来，炎症被认为参与了重度抑郁障碍（MDD）的发病机制。然而，炎症在抑郁症中的详细机制尚未完全了解。本研究采用慢性社会失败应激法（CSDS）建立抑郁小鼠模型，并通过强迫游泳试验和蔗糖偏好试验等行为检查进行证实。海马棘密度和突触后密度蛋白95 （PSD95）的降低进一步验证了抑郁模型。然后观察小胶质细胞极化状态和内质网应激。在转录水平上，CSDS小鼠M1标记物（诱导型一氧化氮合酶（iNOS）、CD16、CD86、CXCL10）高于对照组，M2标记物（精氨酸酶和CD206）在两组间无显著差异。免疫荧光染色观察到CSDS诱导抑郁小鼠海马中增加的活化小胶质细胞与iNOS合并，而不是精氨酸酶。M1标记物白介素(IL)-1β和肿瘤坏死因子(TNF)-α升高，而M1标记物IL-6和M2标记物IL-10不变。csds诱导的抑郁症小鼠内质网应激信号因子，包括蛋白激酶rna样内质网激酶（PERK）、真核翻译起始因子2磷酸化α-亚基（p-eIF2α）、C/EBP同源蛋白（CHOP）和X-box结合蛋白1（XBP1）的表达均显著高于对照组。总之，我们的研究结果表明，M1极化和内质网应激在MDD发病机制中起着至关重要的作用。
Inflammation recently has been considered to be participated in the pathogenesis of major depressive disorder (MDD). However, the detailed mechanism of inflammation in depression has not been completely understood yet. In the present study, depression mice model was established by chronic social defeat stress (CSDS) method and confirmed by behavior examinations including forced swimming test and sucrose preference test. The decrease of spine density and postsynaptic density protein 95 (PSD95) in hippocampus further verified the depression model. Then, the microglia polarization state and endoplasmic reticulum (ER) stress were investigated. At transcriptional level, M1 marker (inducible nitric oxide synthase (iNOS), CD16, CD86, CXCL10) in CSDS mice was higher than that in control group while there was no difference in M2 marker (Arginase and CD206) between two groups. And it was observed in the hippocampus of CSDS induced depression mice that increased activated microglia was merged with iNOS instead of arginase by immunofluorescence staining. Furthermore, the M1 marker Interleukin (IL)-1β and tumor necrosis factor (TNF)-α were increased in depression mice while the M1 marker IL-6 and M2 marker IL-10 remained unchanged. The expression of ER stress signaling factors, including protein kinase RNA-like ER kinase (PERK), Phosphorylated α-subunit of eukaryotic translation initiation factor 2(p-eIF2α), C/EBP homologous protein (CHOP), and X-box binding protein 1(XBP1) were significantly higher in CSDS-induced depression mice than in control mice. In all, our results suggest that M1 polarization and ER stress play a vital role in MDD pathogenesis.