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

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 and Schahram Akbarian ()
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Julong Wei: Wayne State University School of Medicine
Tova Y. Lambert: Friedman Brain Institute Icahn School of Medicine at Mount Sinai
Aditi Valada: Friedman Brain Institute Icahn School of Medicine at Mount Sinai
Nikhil Patel: Wayne State University School of Medicine
Kellie Walker: Wayne State University School of Medicine
Jayna Lenders: Wayne State University School of Medicine
Carl J. Schmidt: University of Michigan School of Medicine
Marina Iskhakova: Friedman Brain Institute Icahn School of Medicine at Mount Sinai
Adnan Alazizi: Wayne State University School of Medicine
Henriette Mair-Meijers: Wayne State University School of Medicine
Deborah C. Mash: University of Miami
Francesca Luca: Wayne State University School of Medicine
Roger Pique-Regi: Wayne State University School of Medicine
Michael J. Bannon: Wayne State University School of Medicine
Schahram Akbarian: Friedman Brain Institute Icahn School of Medicine at Mount Sinai

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41455-8

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