Journal article
Gene expression changes following chronic antipsychotic exposure in single cells from mouse striatum
Molecular psychiatry, Vol.27(6), pp.2803-2812
03/23/2022
DOI: 10.1038/s41380-022-01509-7
PMID: 35322200
Abstract
Schizophrenia is an idiopathic psychiatric disorder with a high degree of polygenicity. Evidence from genetics, single-cell transcriptomics, and pharmacological studies suggest an important, but untested, overlap between genes involved in the etiology of schizophrenia and the cellular mechanisms of action of antipsychotics. To directly compare genes with antipsychotic-induced differential expression to genes involved in schizophrenia, we applied single-cell RNA-sequencing to striatal samples from male C57BL/6 J mice chronically exposed to a typical antipsychotic (haloperidol), an atypical antipsychotic (olanzapine), or placebo. We identified differentially expressed genes in three cell populations identified from the single-cell RNA-sequencing (medium spiny neurons [MSNs], microglia, and astrocytes) and applied multiple analysis pipelines to contextualize these findings, including comparison to GWAS results for schizophrenia. In MSNs in particular, differential expression analysis showed that there was a larger share of differentially expressed genes (DEGs) from mice treated with olanzapine compared with haloperidol. DEGs were enriched in loci implicated by genetic studies of schizophrenia, and we highlighted nine genes with convergent evidence. Pathway analyses of gene expression in MSNs highlighted neuron/synapse development, alternative splicing, and mitochondrial function as particularly engaged by antipsychotics. In microglia, we identified pathways involved in microglial activation and inflammation as part of the antipsychotic response. In conclusion, single-cell RNA sequencing may provide important insights into antipsychotic mechanisms of action and links to findings from psychiatric genomic studies.
Details
- Title: Subtitle
- Gene expression changes following chronic antipsychotic exposure in single cells from mouse striatum
- Creators
- Anthony Abrantes - Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USAPaola Giusti-Rodriguez - University of FloridaNaEshia Ancalade - Department of Genetics, University of North Carolina, Chapel Hill, NC, USAShadia Sekle - Department of Genetics, University of North Carolina, Chapel Hill, NC, USAMarcus L Basiri - Neuroscience Center, University of North Carolina, Chapel Hill, NC, USAGarret D Stuber - University of WashingtonPatrick F Sullivan - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenRainbo Hultman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.27(6), pp.2803-2812
- DOI
- 10.1038/s41380-022-01509-7
- PMID
- 35322200
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Language
- English
- Date published
- 03/23/2022
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984230139102771
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