Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior

Publication date: May 2018Source: Brain, Behavior, and Immunity, Volume 70Author(s): Amanda Crider, Tami Feng, Chirayu D. Pandya, Talisha Davis, Ashwati Nair, Anthony O. Ahmed, Babak Baban, Gustavo Turecki, Anilkumar PillaiAbstractMajor depressive disorder (MDD) is one of the most common and debilitating neuropsychiatric illnesses. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of MDD. The complement system represents one of the major effector mechanisms of the innate immune system, and plays a critical role in inflammation. However, the role of complement components in MDD is not well understood. Here, we found significant increase in component 3 (C3) expression in the prefrontal cortex (PFC) of depressed suicide subjects. We tested the role of altered C3 expression in mouse model of depression and found that increased C3 expression in PFC as a result of chronic stress causes depressive-like behavior. Conversely, mice lacking C3 were resilient to stress-induced depressive-like behavior. Moreover, selective overexpression of C3 in PFC was sufficient to cause depressive-like behavior in mice. We found that C3a (activated product of C3) receptor, C3aR+ monocytes were infiltrated into PFC following chronic stress. However, C3aR knockout mice displayed significantly reduced monocyte recruitment into PFC and reduced levels of the proinflammatory cytokine IL-1β in PFC after chronic stress. In addition, C3aR knockout mice did not exhibit...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research