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Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior

Wohleb, Eric S ; Powell, Nicole D ; Godbout, Jonathan P ; Sheridan, John F

The Journal of neuroscience, 2013-08, Vol.33 (34), p.13820-13833 [Periódico revisado por pares]

United States: Society for Neuroscience

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Título:
Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior
Autor: Wohleb, Eric S ; Powell, Nicole D ; Godbout, Jonathan P ; Sheridan, John F
Assuntos: Animals ; Antigens, CD - metabolism ; Anxiety Disorders - etiology ; Anxiety Disorders - immunology ; Anxiety Disorders - pathology ; Bone Marrow - pathology ; Brain - pathology ; Calcium-Binding Proteins - metabolism ; Cell Movement - genetics ; Cell Movement - immunology ; Cytokines - genetics ; Cytokines - metabolism ; Disease Models, Animal ; Exploratory Behavior ; Gene Expression Regulation ; Green Fluorescent Proteins - genetics ; Macrophages - physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microfilament Proteins - metabolism ; Microglia - physiology ; Monocytes - physiology ; Muramidase - genetics ; Muramidase - metabolism ; Receptors, CCR2 - deficiency ; Receptors, CCR2 - genetics ; Receptors, Interleukin-8A - genetics ; Receptors, Interleukin-8B - deficiency ; Receptors, Interleukin-8B - genetics ; Stress, Psychological - complications ; Stress, Psychological - immunology ; Time Factors
É parte de: The Journal of neuroscience, 2013-08, Vol.33 (34), p.13820-13833
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Author contributions: E.S.W., J.P.G., and J.F.S. designed research; E.S.W. and N.D.P. performed research; E.S.W. and J.F.S. analyzed data; E.S.W., J.P.G., and J.F.S. wrote the paper.
Descrição: 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(+)/SSC(lo)/Ly6C(hi)) and brain macrophages (CD11b(+)/SSC(lo)/CD45(hi)). 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(+) bone marrow (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. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2(KO)) or fractalkine receptor knockout (CX3CR1(KO))] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2(KO) or CX3CR1(KO) donor cells. 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 anxiety.
Editor: United States: Society for Neuroscience
Idioma: Inglês

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Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior

Wohleb, Eric S ; Powell, Nicole D ; Godbout, Jonathan P ; Sheridan, John F

United States: Society for Neuroscience

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