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Authors & Affiliations
Hanna Lemmik, Eugene Kim, Michel Bernanos Soares Mesquita, Wuding Zhou, Laura Westacott, Diana Cash
Abstract
The complement system is an innate immune pathway that responds to pathogens and cellular stress. The complement receptor C3aR is expressed on various brain cells, especially microglia. C3a, the ligand of C3aR, is elevated in several psychiatric disorders, such as psychosis, schizophrenia, bipolar disorder and depression. Previous studies have shown that mice lacking C3aR exhibit behavioural abnormalities, including anxiety, hyperactivity, and working memory deficit. These findings indicate that C3aR is involved in the development and/or function of brain circuits. We performed a brain imaging study using in vivo whole brain structural magnetic resonance imaging (MRI) and blood oxygenation level dependent functional MRI (BOLD fMRI) to characterize the role of C3aR in brain circuit development. We scanned male and female C3ar-/- mice and wild-type littermates (n=68 in total) at two time-points, adolescence (PND30) and adulthood (PND90). Preliminary imaging analysis reveals a higher global functional connectivity (p<0.05, diff=0.3254), and global efficiency (p<0.05, diff=0.159) in C3ar-/- mice in adolescence, both of which normalized by adulthood. We observed no structural changes at either time-point. Future work will focus on seed-based analyses of functional connectivity as well as longitudinal analysis of brain area structure and function to identify which circuits contribute most to the observed changes and how the implicated brain areas change over time. In summary, our study provides novel evidence that C3a/C3aR signalling is involved in brain circuit function in adolescence which is a period of enhanced psychiatric vulnerability due to increased brain plasticity.