Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning.

ABSTRACT: Synapse density is reduced in postmortem cortical tissue from schizophrenia patients, which is suggestive of increased synapse elimination. Using a reprogrammed in vitro model of microglia-mediated synapse engulfment, we demonstrate increased synapse elimination in patient-derived neural cultures and isolated synaptosomes. This excessive synaptic pruning reflects abnormalities in both microglia-like cells and synaptic structures. Further, we find that schizophrenia risk-associated variants within the human complement component 4 locus are associated with increased neuronal complement deposition and synapse uptake; however, they do not fully explain the observed increase in synapse uptake. Finally, we demonstrate that the antibiotic minocycline reduces microglia-mediated synapse uptake in v

SUBMITTER: Sellgren CM 

PROVIDER: S-EPMC6410571 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature