Sympathetic Release of Splenic Monocytes Promotes Recurring Anxiety Following Repeated Social Defeat.
Sympathetic Release of Splenic Monocytes Promotes Recurring Anxiety Following Repeated Social Defeat.
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DOI：
10.1016/j.biopsych.2015.07.010
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发表时间：
2016-05-15
影响因子：
10.6
通讯作者：
Sheridan JF
中科院分区：
文献类型：
--
作者：
McKim DB;Patterson JM;Wohleb ES;Jarrett BL;Reader BF;Godbout JP;Sheridan JF
Neuroinflammatory signaling may contribute to the pathophysiology of chronic anxiety disorders. Previous work showed that repeated social defeat (RSD) in mice promoted stress-sensitization that was characterized by the recurrence of anxiety following sub-threshold stress 24 days after RSD. Furthermore, splenectomy following RSD prevented the recurrence of anxiety in stress-sensitized (SS) mice. We hypothesize that the spleen of RSD-exposed mice became a reservoir of primed monocytes that were released following neuroendocrine activation by sub-threshold stress. Mice were subjected to sub-threshold stress (i.e., single cycle of social defeat) 24 days after RSD, and immune and behavioral measures were taken. Sub-threshold stress 24 days after RSD re-established anxiety-like behavior that was associated with egress of Ly6Chi monocytes from the spleen. Moreover, splenectomy prior to RSD blocked monocyte trafficking to the brain and prevented anxiety-like behavior following sub-threshold stress. Splenectomy, however, had no effect on monocyte accumulation or anxiety when determined 14 hours after RSD. In addition, splenocytes cultured 24 days after RSD exhibited a primed inflammatory phenotype. Peripheral sympathetic inhibition prior to sub-threshold stress blocked monocyte trafficking from the spleen to the brain and prevented the re-establishment of anxiety in RSD-sensitized mice. Last, β-adrenergic antagonism also prevented splenic monocyte egress after acute stress. The spleen served as a unique reservoir of primed monocytes that were readily released following sympathetic activation by sub-threshold stress that promoted the re-establishment of anxiety. Collectively, the long-term storage of primed monocytes in the spleen may have a profound influence on recurring anxiety disorders.
