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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Nature Portfolio
2023-09-01
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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. |
first_indexed | 2024-03-10T17:34:10Z |
format | Article |
id | doaj.art-0b94c40b089d4e7e910d07aeeea33a7f |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-10T17:34:10Z |
publishDate | 2023-09-01 |
publisher | Nature Portfolio |
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series | Nature Communications |
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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