Depletion of Microglia Attenuates Dendritic Spine Loss and Neuronal Apoptosis in the Acute Stage of Moderate Traumatic Brain Injury in Mice
Depletion of Microglia Attenuates Dendritic Spine Loss and Neuronal Apoptosis in the Acute Stage of Moderate Traumatic Brain Injury in Mice
复制标题
小胶质细胞的消耗减轻了小鼠中度创伤性脑损伤急性期的树突棘丢失和神经元凋亡
DOI：
10.1089/neu.2019.6460
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发表时间：
2019-09-18
影响因子：
4.2
通讯作者：
Li, Wei-ping
中科院分区：
文献类型：
--
作者：
Wang, Chuan-fang;Zhao, Cheng-cheng;Li, Wei-ping
小胶质细胞是中枢神经系统的主要免疫细胞，在创伤性脑损伤后会发生显著的形态和转录变化。然而，它们在脑外伤发病机制中的确切作用仍存在争议，有待阐明。在本研究中，THY-1 GFP小鼠连续21天接受集落刺激因子1受体抑制剂(PLX3397)治疗，然后造成中度液压冲击伤(FPI)。分别于伤后1d和3d取脑标本进行流式细胞仪分析、免疫荧光、树突棘定量、末端脱氧核苷酸转移酶dUTP缺口末端标记法和Western印迹分析。我们发现，PLX3397治疗显著降低了常驻小胶质细胞和浸润性免疫细胞的百分比。小胶质细胞的耗竭促进了脑损伤后突起的生长，保留了树突棘，减少了脑细胞和神经元的总凋亡率，同时伴随着内质网应激标志蛋白、C/EBP同源蛋白和肌醇需求蛋白-1α蛋白水平的降低。综上所述，这些发现表明，小胶质细胞的耗竭可能在FPI的急性期发挥有益的影响。
Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1 alpha. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.