MAJOR DEPRESSIVE DISORDER AND SUICIDE: IS LOCAL MICROGLIAL COMPLEMENT COMPONENT RNA EXPRESSION INVOLVED?

Complement signalling is instrumental to synaptic plasticity. The classical complement cascade is initiated by the complement component (C)1 complex, where the C1q subunit acts as a tag for synaptic pruning by microglia. Complement synaptic regulation is increasingly implicated in the pathophysiology of major depressive disorder (MDD) and suicide. C1q RNA is enriched in microglial processes compared to the soma in rodents, indicating local translation may be required for synaptic tagging by microglial processes. Whether this spatial distribution is conserved humans remains unknown. We investigated the expression and subcellular localization of complement components in post-mortem dorsolateral prefrontal cortex (dlPFC) samples (Douglas-Bell Canada Brain Bank) from young individuals (ages 9-32) with MDD who died by suicide. Using combined fluorescence in situ hybridization (FISH; RNAScope) and immunofluorescence, we examined the expression of the C1q subunit C1qc in relation to the microglial/macrophage marker ionized calcium-binding adapter molecule 1 (IBA1). Preliminary observations demonstrate that C1qc is expressed in both the soma and the ramified processes of IBA1+ cells, as well as within IBA1+ clusters, supporting the hypothesis of localized translation. C1qc expression was also detected in perivascular DAPI+/IBA1- cells, suggesting that additional cell types contribute to complement signaling in the human dlPFC. Ongoing analyses are quantifying the frequency of IBA1+ process RNA expression and comparing it across MDD and and matched sudden-death controls. Our results aid in characterizing the contribution of microglial local translation in the neurobiology of depression and suicide.