Single Nuclei Transcriptomics in Human and Non-human Primate Striatum in Opioid Use Disorder

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 31

PMID 38296993

Authors

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

Ryan W Logan

Affiliations

Soon will be listed here.

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.

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