NYMC Faculty Publications
Activated Microglia Cause Metabolic Disruptions in Developmental Cortical Interneurons that Persist in Interneurons from Individuals with Schizophrenia
DOI
10.1038/s41593-020-00724-1
Journal Title
Nature Neuroscience
First Page
1352
Last Page
1364
Document Type
Article
Publication Date
11-2020
Department
Pathology, Microbiology and Immunology
Second Department
Biostatistics
Third Department
Cell Biology and Anatomy
Abstract
The mechanisms by which prenatal immune activation increase the risk for neuropsychiatric disorders are unclear. Here, we generated developmental cortical interneurons (cINs)-which are known to be affected in schizophrenia (SCZ) when matured-from induced pluripotent stem cells (iPSCs) derived from healthy controls (HCs) and individuals with SCZ and co-cultured them with or without activated microglia. Co-culture with activated microglia disturbed metabolic pathways, as indicated by unbiased transcriptome analyses, and impaired mitochondrial function, arborization, synapse formation and synaptic GABA release. Deficits in mitochondrial function and arborization were reversed by alpha lipoic acid and acetyl-L-carnitine treatments, which boost mitochondrial function. Notably, activated-microglia-conditioned medium altered metabolism in cINs and iPSCs from HCs but not in iPSCs from individuals with SCZ or in glutamatergic neurons. After removal of activated-microglia-conditioned medium, SCZ cINs but not HC cINs showed prolonged metabolic deficits, which suggests that there is an interaction between SCZ genetic backgrounds and environmental risk factors.
Recommended Citation
Park, G., Yin, C., Huang, W., Kim, H., & Chung, S. (2020). Activated Microglia Cause Metabolic Disruptions in Developmental Cortical Interneurons that Persist in Interneurons from Individuals with Schizophrenia. Nature Neuroscience, 23 (11), 1352-1364. https://doi.org/10.1038/s41593-020-00724-1
Comments
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