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

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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.