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

Amanda Crider, Tami Feng, Chirayukumar D Pandya, Talisha Davis, Ashwati Nair, Anthony O. Ahmed, Babak Baban, Gustavo Turecki, Anilkumar R Pillai

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Major 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 chronic stress-induced behavior despair. Similarly, chronic stress-induced increases in C3aR+ monocytes and IL-1β in PFC, and depressive-like behavior were attenuated by myeloid cell depletion. These postmortem and preclinical studies identify C3aR signaling as a key factor in MDD pathophysiology.

Original languageEnglish (US)
Pages (from-to)246-256
Number of pages11
JournalBrain, Behavior, and Immunity
Volume70
DOIs
StatePublished - May 1 2018

Fingerprint

Complement C3a
Prefrontal Cortex
Monocytes
Major Depressive Disorder
Interleukin-1
Knockout Mice
Immune System
Myeloid Cells
Suicide
Depression
Cytokines
Inflammation

Keywords

  • Animals
  • Behavior
  • C3
  • Complement
  • Depression

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior. / Crider, Amanda; Feng, Tami; Pandya, Chirayukumar D; Davis, Talisha; Nair, Ashwati; Ahmed, Anthony O.; Baban, Babak; Turecki, Gustavo; Pillai, Anilkumar R.

In: Brain, Behavior, and Immunity, Vol. 70, 01.05.2018, p. 246-256.

Research output: Contribution to journalArticle

Crider, Amanda ; Feng, Tami ; Pandya, Chirayukumar D ; Davis, Talisha ; Nair, Ashwati ; Ahmed, Anthony O. ; Baban, Babak ; Turecki, Gustavo ; Pillai, Anilkumar R. / Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior. In: Brain, Behavior, and Immunity. 2018 ; Vol. 70. pp. 246-256.
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