Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder

Abstract Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids...

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Main Authors: Julong Wei, Tova Y. Lambert, Aditi Valada, Nikhil Patel, Kellie Walker, Jayna Lenders, Carl J. Schmidt, Marina Iskhakova, Adnan Alazizi, Henriette Mair-Meijers, Deborah C. Mash, Francesca Luca, Roger Pique-Regi, Michael J. Bannon, Schahram Akbarian
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41455-8
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author Julong Wei
Tova Y. Lambert
Aditi Valada
Nikhil Patel
Kellie Walker
Jayna Lenders
Carl J. Schmidt
Marina Iskhakova
Adnan Alazizi
Henriette Mair-Meijers
Deborah C. Mash
Francesca Luca
Roger Pique-Regi
Michael J. Bannon
Schahram Akbarian
author_facet Julong Wei
Tova Y. Lambert
Aditi Valada
Nikhil Patel
Kellie Walker
Jayna Lenders
Carl J. Schmidt
Marina Iskhakova
Adnan Alazizi
Henriette Mair-Meijers
Deborah C. Mash
Francesca Luca
Roger Pique-Regi
Michael J. Bannon
Schahram Akbarian
author_sort Julong Wei
collection DOAJ
description Abstract Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 − 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry.
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spelling doaj.art-0b94c40b089d4e7e910d07aeeea33a7f2023-11-20T09:54:57ZengNature PortfolioNature Communications2041-17232023-09-0114111310.1038/s41467-023-41455-8Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorderJulong Wei0Tova Y. Lambert1Aditi Valada2Nikhil Patel3Kellie Walker4Jayna Lenders5Carl J. Schmidt6Marina Iskhakova7Adnan Alazizi8Henriette Mair-Meijers9Deborah C. Mash10Francesca Luca11Roger Pique-Regi12Michael J. Bannon13Schahram Akbarian14Center for Molecular Medicine and Genetics, Wayne State University School of MedicineDepartment of Psychiatry, Department of Neuroscience and Department of Genetics and Genomic Sciences, Friedman Brain Institute Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Department of Neuroscience and Department of Genetics and Genomic Sciences, Friedman Brain Institute Icahn School of Medicine at Mount SinaiDepartment of Pharmacology, Wayne State University School of MedicineDepartment of Pharmacology, Wayne State University School of MedicineDepartment of Pharmacology, Wayne State University School of MedicineDepartment of Pathology, University of Michigan School of MedicineDepartment of Psychiatry, Department of Neuroscience and Department of Genetics and Genomic Sciences, Friedman Brain Institute Icahn School of Medicine at Mount SinaiCenter for Molecular Medicine and Genetics, Wayne State University School of MedicineCenter for Molecular Medicine and Genetics, Wayne State University School of MedicineDepartment of Neurology, Miller School of Medicine, University of MiamiCenter for Molecular Medicine and Genetics, Wayne State University School of MedicineCenter for Molecular Medicine and Genetics, Wayne State University School of MedicineDepartment of Pharmacology, Wayne State University School of MedicineDepartment of Psychiatry, Department of Neuroscience and Department of Genetics and Genomic Sciences, Friedman Brain Institute Icahn School of Medicine at Mount SinaiAbstract Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 − 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain’s reward circuitry.https://doi.org/10.1038/s41467-023-41455-8
spellingShingle Julong Wei
Tova Y. Lambert
Aditi Valada
Nikhil Patel
Kellie Walker
Jayna Lenders
Carl J. Schmidt
Marina Iskhakova
Adnan Alazizi
Henriette Mair-Meijers
Deborah C. Mash
Francesca Luca
Roger Pique-Regi
Michael J. Bannon
Schahram Akbarian
Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
Nature Communications
title Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
title_full Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
title_fullStr Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
title_full_unstemmed Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
title_short Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
title_sort single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder
url https://doi.org/10.1038/s41467-023-41455-8
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