Synaptic elimination during adolescence may be increased in schizophrenia (SCZ). Sellgren et al. generated induced microglia (iMGs) and induced neurons from healthy controls (HCs) and individuals with SCZ, and imaged iMGs co-cultured with synaptosomes (SYNs) purified from the neurons. SCZ-derived iMGs phagocytosed more SYNs than did HC-derived iMGs, and this was partly explained by genetic variation in the complement 4 locus. Pretreatment of iMGs with minocycline reduced SYN uptake, and health records revealed that individuals who were chronically exposed to minocycline or the related doxycyline during adolescence were slightly less likely to develop SCZ.
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Sellgren, C. M. et al. Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat. Neurosci. https://doi.org/10.1038/s41593-018-0334-7 (2019)
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Bray, N. Overpruning in schizophrenia. Nat Rev Neurosci 20, 191 (2019). https://doi.org/10.1038/s41583-019-0144-2
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DOI: https://doi.org/10.1038/s41583-019-0144-2