Complement receptor C3ar1 deficiency does not alter brain structure or functional connectivity across early life development
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Previous studies suggest that genetic deletion of the complement C3a anaphylatoxin chemotactic receptor ( C3ar1 ), a key component of the innate immune response, influences behaviours associated with psychiatric symptomatology in mice but when and where C3ar1 is needed in the brain is not known. These questions are significant because, as a G-protein-coupled receptor (GPCR), human C3AR1 serves as a potential therapeutic target for disorders associated with complement dysregulation, such as schizophrenia. To provide a brain-wide assessment of developmental C3ar1 activity, we used longitudinal tensor-based morphometry (TBM), fractional anisotropy (FA) from diffusion-weighted magnetic resonance imaging (dMRI) and blood oxygen-level dependent functional MRI (BOLD fMRI) in male and female C3ar1 -deficient mice and wild-type littermates, with behavioural assessment in adulthood. Unexpectedly, we did not find robust C3ar1 -dependent phenotype in any of these measures. Therefore, our study does not support neurodevelopmental hypotheses for C3ar1 which will likely have implications for targeting this receptor in disease.
