Gene expression changes following chronic antipsychotic exposure in single cells from mouse striatum.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
07
07
2021
accepted:
23
02
2022
revised:
10
02
2022
pubmed:
25
3
2022
medline:
3
6
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35322200
doi: 10.1038/s41380-022-01509-7
pii: 10.1038/s41380-022-01509-7
doi:
Substances chimiques
Antipsychotic Agents
0
Benzodiazepines
12794-10-4
RNA
63231-63-0
Haloperidol
J6292F8L3D
Olanzapine
N7U69T4SZR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2803-2812Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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