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Studies of the relationship between organic functional disorders induced by chronic psychological stress and bone marrow-derived microglia

慢性心理应激所致器质性功能障碍与骨髓源性小胶质细胞关系的研究

基本信息

批准号：
22590661
负责人：
ATAKA Koji
金额：
$ 2.83万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic psychological stress. Bone marrow derived-microglia are CX3CR1lowCCR2+CXCR4high, as distinct from CX3CR1highCCR2-CXCR4low resident microglia, and express higher levels of interleukin-1β but lower levels of tumor necrosis factor-α. Chronic psychological stress stimulates the expression of monocyte chemotactic protein-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4+ monocytes in peripheral circulation. And a chemokine (C-C motif) receptor (CCR)2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. In conclusion chronic psychological stress induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the β3-adrenergic pathway and the CCR2/MCP-1 axis are involved in this mechanism.

在这里，我们发现骨髓来源的小胶质细胞特异性地浸润接受慢性心理应激的小鼠的室旁核（PVN）。骨髓来源的小胶质细胞为 CX3CR1lowCCR2+CXCR4high，与 CX3CR1highCCR2-CXCR4low 常驻小胶质细胞不同，表达较高水平的白介素-1β，但表达较低水平的肿瘤坏死因子-α。慢性心理应激刺激PVN神经元中单核细胞趋化蛋白-1的表达，减少骨髓中的基质细胞衍生因子-1（SDF-1）并增加外周循环中CXCR4+单核细胞的频率。趋化因子（C-C 基序）受体 (CCR)2 或 β3-肾上腺素受体阻断剂可防止 PVN 中骨髓来源的小胶质细胞的浸润。总之，慢性心理应激诱导骨髓源性小胶质细胞向PVN浸润，可以想象β3-肾上腺素能通路和CCR2/MCP-1轴参与了这一机制。