C3aR-dependent infiltrating monocytes promote stress-induced depressive behavior in mice (P4.189)

Objective: NA Background: While depression is both debilitating and widespread, the mechanisms of its disease process are still under investigation. Increasing evidence implicates irregularities in the immune system. In the CNS, the complement system of innate immunity plays a role in several processes that become pathological in depression, including synaptic pruning and cytokine regulation. However, no direct investigations have been made into complement activation in depression. Design/Methods: As previous results from our lab indicated a strong relationship between complement component 3a (C3a) and stress in a mouse model, this study furthered our line of research by using C3a receptor (C3aR) global knockout mice to explore the role of C3aR in the induction of depressive behaviors. We subjected mice to 3 weeks of Chronic Unpredictable Stress (CUS) and subsequent behavioral testing before the acquisition of PFC and hippocampus samples. Results: In behavioral tests, chronic stress induced a significant increase (p Conclusions: As cytokine-secreting activated monocytes have been implicated in the pathogenesis of stress-induced behaviors, the data suggest that removal of monocyte C3aR signaling provides a protective effect. A possible link between the complement system and depression promotes a novel understanding of neuroimmunological system interplay in stress and potential identification of drug targets for the future treatment of depression. Study Supported by: Medical Scholars Program at the Medical College of Georgia Disclosure: Dr. Feng has nothing to disclose. Dr. Davis has nothing to disclose. Dr. Baban has nothing to disclose. Dr. Pillai has nothing to disclose.