Talk abstracts
Talk on Wednesday 04:45-05:00pm submitted by Daniel McKim
Sympathetic Release of Splenic Monocytes Promotes Recurring Anxiety Following Repeated Social Defeat
Daniel B. McKim (Neuroscience Graduate Program), Jenna M. Patterson (Neuroscience), Eric S. Wohleb (Yale University), Brant L. Jarrett Biosciences - COD (Brenda Reader Biosciences - COD), Jonathan P. Godbout (Neuroscience), John F. Sheridan (Biosciences - College of Dentistry)
Abstract:
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. 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 and prevented the recurrence of anxiety-like behavior in sensitized mice. 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. Next, treatment with a peripheral sympathetic inhibitor prior to sub-threshold stress blocked monocyte redistribution and prevented the re-establishment of anxiety in RSD-sensitized mice. Additionally, increased availability of releasable monocyte was associated with monocyte-progenitor proliferation within the spleen. Collectively, these data show that the spleen is capable of producing and storing primed monocytes that promote exaggerated behavioral responses to acute stress, even many days after a sensitizing event.
Keywords: Stress, Monocytes, Neuroimmunology