Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder

BaDoi N. Phan, Madelyn H. Ray, Xiangning Xue, Chen Fu, Robert J. Fenster, Stephen J. Kohut, Jack Bergman, Suzanne N. Haber, Kenneth M. McCullough, Madeline K. Fish, Jill R. Glausier, Qiao Su, Allison E. Tipton, David A. Lewis, Zachary Freyberg, George C. Tseng, Shelley J. Russek, Yuriy Alekseyev, Kerry J. Ressler, Marianne L. Seney, Andreas R. Pfenning () and Ryan W. Logan ()
Additional contact information
BaDoi N. Phan: Carnegie Mellon University
Madelyn H. Ray: Boston University School of Medicine
Xiangning Xue: University of Pittsburgh
Chen Fu: University of Massachusetts Chan Medical School
Robert J. Fenster: Harvard Medical School
Stephen J. Kohut: Harvard Medical School
Jack Bergman: Harvard Medical School
Suzanne N. Haber: Harvard Medical School
Kenneth M. McCullough: Harvard Medical School, McLean Hospital
Madeline K. Fish: Boston University
Jill R. Glausier: University of Pittsburgh School of Medicine
Qiao Su: Carnegie Mellon University
Allison E. Tipton: Boston University
David A. Lewis: University of Pittsburgh School of Medicine
Zachary Freyberg: University of Pittsburgh School of Medicine
George C. Tseng: University of Pittsburgh
Shelley J. Russek: Boston University School of Medicine
Yuriy Alekseyev: Boston University School of Medicine
Kerry J. Ressler: Harvard Medical School
Marianne L. Seney: University of Pittsburgh School of Medicine
Andreas R. Pfenning: Carnegie Mellon University
Ryan W. Logan: Boston University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction is linked to psychiatric disorders, including opioid use disorder (OUD). Striatal subregions are divided based on neuroanatomy, each with unique roles in OUD. In OUD, the dorsal striatum is involved in altered reward processing, formation of habits, and development of negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) and less abundant cell populations (e.g., interneurons) in human dorsal striatum. Pathways related to neurodegeneration, interferon response, and DNA damage were significantly enriched in striatal neurons of individuals with OUD. DNA damage markers were also elevated in striatal neurons of opioid-exposed rhesus macaques. Sex-specific molecular differences in glial cell subtypes associated with chronic stress were found in OUD, particularly female individuals. Together, we describe different cell types in human dorsal striatum and identify cell type-specific alterations in OUD.

Date: 2024
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DOI: 10.1038/s41467-024-45165-7

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