Stress-induced recruitment of peripheral macrophages to the brain promotes anxiety-like behavior
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Series/Report no.:2013 Edward F. Hayes Graduate Research Forum. 27th
Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b+/Ly6Chi) and brain macrophages (CD11b+/CD45hi). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP+ and GFP+ BM-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP+ mice showed that RSD increased recruitment of GFP+ macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP+ macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP+ BM-chimeric mice. Last, mice deficient in chemokine receptors associated with monocyte trafficking, chemokine receptor-2 (CCR2KO) or fractalkine receptor (CX3CR1KO), failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of stress-induced anxiety.
Social and Behavioral Sciences; Social Work; Law: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
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