THE INVOLVEMENT OF SPLENIC IMMUNE CELLS IN THE DEPRESSION-LIKE BEHAVIORS INDUCED BY CHRONIC SOCIAL DEFEAT STRESS

Abstract Background Accumulating evidences suggest a substantial role of enhanced inflammatory responses in the pathophysiology of major depressive disorder (MDD). The spleen, a pivotal organ in the immune response, may play a role in the enhanced inflammatory responses of MDD. Chronic social defeat stress (CSDS) is well established to develop an animal model of MDD. Aims & Objectives In the present study, we investigated the involvement of the spleen in the CSDS-induced depression-like behaviors in mouse. Method In the CSDS, the adult C57BL/6J mouse was exposed to an aggressor ICR mouse for 10 consecutive days. Results CSDS effectively reduced the social interaction (SI) ratios in the social interaction test (SIT) and the time spent in the open arms in the elevated plus maze test (EPM) in C57BL/6J mouse. A remarkable observation was the significant increase in the spleen weight following CSDS, suggesting enhanced inflammatory response in the splenic immune cells. Splenectomy ameliorated the CSDS-induced social impairment in the SIT but not anxiety-like behavior in the EPM. CSDS elevated the levels of noradrenaline (NA) in the spleen. Interestingly, CSDS reduced the adrenergic β2 receptors, primarily localized on CD4+ T cells. Flow cytometry analysis revealed that CSDS decreased CD4+ T cells, but increased CD11b+Ly6C+ monocytes in the spleen. Antidepressant treatment significantly ameliorated the increase of CD11b+ Ly6C+ monocytes and social impairment induced by CSDS. Discussion&Conclusion: These findings provide insights into the role of splenic immune cells in depressive-like behavior induced by CSDS. Furthermore, our results suggest that a decreased noradrenergic anti-inflammatory pathway may be implicated in the depression-like behavior induced by CSDS.