Faculty, Staff and Student Publications
Publication Date
11-1-2025
Journal
Molecular Psychiatry
DOI
10.1038/s41380-025-03097-8
PMID
40640554
PMCID
PMC12532727
PubMedCentral® Posted Date
7-10-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The social deficits following chronic stress conditions are linked to synaptic dysfunction in the brain. Complement system plays a critical role in synapse regulation. Although complement has been implicated in chronic stress-induced behavior deficits the cellular substrates and mechanisms underlying complement-mediated behavior changes under chronic stress conditions are not known. In the present study, we investigated the role of complement component 3a receptor (C3ar1) in microglia and monocytes/macrophages (Mo/MΦ) in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found that deletion of microglial C3ar1 attenuated stress-induced social behavior deficits and changes in neuroinflammatory as well as synaptic markers in the prefrontal cortex (PFC). RNA sequencing data revealed that microglial C3ar1 deletion attenuates CUS-mediated changes in the expression of immediate-early genes such as Fos and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. In contrast, lack of C3ar1 in Mo/MΦ induced social behavior deficits. Together, these findings indicate opposite functions of C3ar1 signaling in microglia and Mo/MΦ under chronic stress conditions.
Keywords
Animals, Microglia, Mice, Stress, Psychological, Signal Transduction, Prefrontal Cortex, Receptors, Complement, Male, Macrophages, Mice, Inbred C57BL, Synapses, Social Behavior, Mice, Knockout, Behavior, Animal, Brain, Neuroscience, Depression
Published Open-Access
yes
Recommended Citation
Tripathi, Ashutosh; Bartosh, Alona; Jose, Dania; et al., "Opposing Roles of Microglial and Macrophagic C3ar1 Signaling in Stress-Induced Synaptic and Behavioral Changes" (2025). Faculty, Staff and Student Publications. 797.
https://digitalcommons.library.tmc.edu/uthshis_docs/797