Changes in the complement system are involved in synaptic pruning in major depressive disorder

The complement system is a set of membrane-bound and circulating proteins (predominantly synthesized in the liver), whose function is to warn of a microbial invasion (as do the receptors for pathogens and damage-associated molecular patterns, PAMPs and DAMPs, respectively) and initiate the defense response, by tagging foreign or self-entities with C3 fragments, promoting phagocytosis and lysis of the membrane of the "invading" organisms. This system is also used by some tissues for structural reorganization, to induce and remove apoptotic cells. In the central nervous system (CNS), synapses are constantly undergoing remodeling via the elimination and formation of new synapses, which is mediated, in part, by complement system proteins produced by microglia and astrocytes. This elimination process (synaptic pruning) appears to be particularly pronounced in neurodegenerative diseases. In this short review, we aim to discuss the role of the complement system in the CNS, particularly in the very prevalent psychiatric disorder, major depressive disorder, emphasizing the importance of astrocytes, as well as the need to advance our understanding of the specificities of the glial complement system proteins for diagnostic and therapeutic purposes.