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Cited by 786

The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.

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

Open access
Sellgren, Carl M., Gracias, Jessica, Watmuff, Bradley, Biag, Jonathan D., Thanos, Jessica M., Whittredge, Paul B., Fu, Ting, Worringer, Kathleen, Brown, Hannah E., Wang, Jennifer, Kaykas, Ajamete, Karmacharya, Rakesh, Goold, Carleton P., Sheridan, Steven D., Perlis, Roy H.·2019·Nature Neuroscience
DOI 10.1038/s41593-018-0334-7
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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 vitro and its use is associated with a modest decrease in incident schizophrenia risk compared to other antibiotics in a cohort of young adults drawn from electronic health records. These findings point to excessive pruning as a potential target for delaying or preventing the onset of schizophrenia in high-risk individuals. Postmortem studies indicate reduced synaptic density in schizophrenia. Sellgren et al. show increased synaptic pruning in patient-derived cell models and provide evidence that C4 risk variants increase engulfment, while minocycline decreases it.

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Metadata

Authors
Sellgren, C. M., Gracias, J., Watmuff, B., Biag, J. D., Thanos, J. M., Whittredge, P. B., Fu, T., Worringer, K., Brown, H. E., Wang, J., Kaykas, A., Karmacharya, R., Goold, C. P., Sheridan, S. D., & Perlis, R. H.
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2019-02-04
Volume
22
Issue
3
Pages
374-385
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-018-0334-7
OpenAlex
W2911701742
Cited by
786
References
68
FWCI
33.68
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. https://app.cochat.ai/papers/10.1038/s41593-018-0334-7
The paper
Sellgren, C. M., Gracias, J., Watmuff, B., Biag, J. D., Thanos, J. M., Whittredge, P. B., Fu, T., Worringer, K., Brown, H. E., Wang, J., Kaykas, A., Karmacharya, R., Goold, C. P., Sheridan, S. D., & Perlis, R. H. (2019). Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nature Neuroscience. https://doi.org/10.1038/s41593-018-0334-7

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.