Poster abstracts
Poster number 12 submitted by Damon DiSabato
Paired Fighting Causes Social Withdrawal and Leukocyte Recruitment to the Cerebral Ventricle in an IL-1R1-dependent Manner
Damon DiSabato (Neuroscience Graduate Program), Danny Nemeth (Division of Biosciences, College of Dentistry), Xiaoyu Liu (Division of Biosciences, College of Dentistry), Braedan Oliver (Institute for Behavioral Medicine Research, College of Medicine), Jonathan Godbout (Department of Neuroscience, College of Medicine), Ning Quan (Division of Biosciences, College of Dentistry)
Abstract:
Chronic stress is associated with an increase in prevalence of mental health complications such as anxiety and depression. We have previously reported that repeated social defeat (RSD) causes microglial activation, monocyte infiltration into the brain, and increased interleukin-1b (IL-1b) signaling in association with prolonged anxiety-like behavior. We hypothesized that IL-1b signaling in the brain was the key player in this stress-mood disorder interaction. In the present study, we used a modified paired fighting (PF) social stress paradigm to induce social stress. Following exposure to six days of PF, C57BL/6 mice displayed general withdrawal in a social interactivity test with juvenile C57BL/6 mice. The experimental mice also experienced a percent decrease in spontaneous alternations in the Y-maze, a measure of functional working memory. PF mice had increases in neutrophils and Ly6Chi reactive monocytes in circulation, and an increased number of peripherally-derived leukocytes in the cerebral ventricle. To examine the significance of IL-1 signaling in these processes, we used our genetic model of global IL-1 receptor 1 knockout, the IL-1 receptor restore model (IL-1R1r/r). After PF, IL-1R1r/r mice did not display the same social withdrawal or reduced spontaneous alternations in the Y-maze. In addition, IL-1R1 deletion did not prevent the increase in circulating Ly6Chi monocytes after PF, but it did reduce the number of peripheral leukocytes in the cerebral ventricle. Next, we repeated the PF protocol with vGlu2Cre-IL-1R1f/f mice, in which IL-1R1 has been deleted only on glutamatergic neurons. Following PF, vGlu2Cre-IL-1R1f/f mice show microglial morphological alterations and monocyte infiltration. However, these mice do not display behavioral changes after PF. Taken together, these results show that neuronal IL-1R1 signaling plays a crucial role in stress-induced affective behavior.
Keywords: Stress, Interleukin-1, Anxiety