Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses
Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses
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小胶质细胞的丢失导致不同类型的慢性压力引起的重度抑郁症的发展
DOI：
10.1007/s11064-017-2270-4
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Chao Huang
中科院分区：
文献类型：
--
作者：
Lijuan Tong;Yu Gong;Peng Wang;Wenfeng Hu;Jili Wang;Zhuo Chen;Wei Zhang;Chao Huang
最近，据报道，慢性不可预测应激（CUS）引起的海马小胶质细胞的丧失和营养不良可介导小鼠重度抑郁症的发生，这些小鼠的小胶质细胞被增强型绿色荧光蛋白连接的CX3C受体1型标记。然而，这种情况是否发生在没有遗传干预的内源性小胶质细胞中仍不清楚。在这里，我们在接受不同类型慢性压力（包括 CUS、慢性束缚压力（CRS）和慢性社交挫败压力（CSDS））治疗的小鼠中解决了这个问题。结果表明，CUS、CRS 和 CSDS 处理显着减少了内源性海马而非皮质小胶质细胞的细胞数量、突起长度、胞体面积和激活标记。给小鼠施用两种经典的小胶质细胞刺激剂脂多糖（LPS）或巨噬细胞集落刺激因子（M-CSF），逆转了CUS、CRS和CSDS诱导的内源性海马小胶质细胞数量的减少，并且还改善了CUS、CRS或CSDS诱导的行为异常，包括强迫游泳试验和悬尾试验中不动时间的增加、蔗糖偏好的抑制以及在空旷场地中心花费的时间减少。此外，米诺环素预处理抑制海马小胶质细胞的初始激活也逆转了海马小胶质细胞数量的减少以及 CUS、CRS 和 CSDS 治疗引起的行为异常。这些结果提供了令人信服的证据，表明不同类型的慢性压力可以引发内源性海马小胶质细胞的丧失，而小胶质细胞数量的恢复可能对重度抑郁症具有治疗价值。
Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS). Results showed that the cellular numbers, process lengths, soma areas and activation markers of endogenous hippocampal but not cortical microglia, were markedly reduced by CUS, CRS and CSDS treatment. Administration of mice with two classical stimulators of microglia, lipopolysaccharide (LPS) or macrophage colony-stimulating factor (M-CSF), reversed the CUS-, CRS- and CSDS-induced reductions in endogenous hippocampal microglial numbers, and also improved the CUS-, CRS- or CSDS-induced behavioral abnormalities, including the increases in the immobile time in the forced swimming test and tail suspension test, the inhibition of sucrose preference, and the decrease in the time spent in the center of open field. Furthermore, inhibition of the initial activation of hippocampal microglia by minocycline pretreatment also reversed the reduction in hippocampal microglial numbers as well as the behavioral abnormalities induced by CUS, CRS and CSDS treatment. These results provide compelling evidences to show that different types of chronic stresses can trigger the loss of endogenous hippocampal microglia and restoration of microglial numbers may have therapeutic values in major depression.
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DOI：
10.1007/978-3-319-77525-8_100075
发表时间：
2018-12
期刊：
Encyclopedia of Big Data Technologies
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
通讯作者：
--
DOI：
10.1210/jcem.85.1.6229
发表时间：
2000
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1109/icmas.2000.858517
发表时间：
2000-07
期刊：
Proceedings Fourth International Conference on MultiAgent Systems
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jones OD;Schall JD;Shen FX
通讯作者：
Shen FX