Cell type-specific multi-omics analysis of cocaine use disorder in the human caudate nucleus

Lea Zillich (), Annasara Artioli, Veronika Pohořalá, Eric Zillich, Laura Stertz, Hanna Belschner, Ammar Jabali, Josef Frank, Fabian Streit, Diana Avetyan, Maja P. Völker, Svenja Müller, Anita C. Hansson, Thomas D. Meyer, Marcella Rietschel, Julia Ladewig, Rainer Spanagel, Ana M. M. Oliveira, Consuelo Walss-Bass, Rick E. Bernardi, Philipp Koch and Stephanie H. Witt
Additional contact information
Lea Zillich: Heidelberg University
Annasara Artioli: Heidelberg University
Veronika Pohořalá: Heidelberg University
Eric Zillich: Heidelberg University
Laura Stertz: University of Texas Health Science Center at Houston
Hanna Belschner: Heidelberg University
Ammar Jabali: Heidelberg University
Josef Frank: Heidelberg University
Fabian Streit: Heidelberg University
Diana Avetyan: Heidelberg University
Maja P. Völker: Heidelberg University
Svenja Müller: Heidelberg University
Anita C. Hansson: Heidelberg University
Thomas D. Meyer: University of Texas Health Science Center at Houston
Marcella Rietschel: Heidelberg University
Julia Ladewig: Heidelberg University
Rainer Spanagel: partner site Mannheim/Heidelberg/Ulm
Ana M. M. Oliveira: partner site Mannheim/Heidelberg/Ulm
Consuelo Walss-Bass: University of Texas Health Science Center at Houston
Rick E. Bernardi: Heidelberg University
Philipp Koch: Heidelberg University
Stephanie H. Witt: Heidelberg University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Structural and functional alterations in the brain’s reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 30,030 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells. We observed 1485 differentially regulated genes and 10,342 differentially accessible peaks, with alterations in MSNs and astrocytes related to neurotransmitter activity and synapse organization. Gene regulatory network analysis identified transcription factors including ZEB1 as exhibiting distinct CocUD-specific subclusters, activating downstream expression of ion- and calcium-channels in MSNs. Further, PDE10A emerged as a potential drug target, showing conserved effects in a rat model. This study highlights cell type-specific molecular alterations in CocUD and provides targets for further investigation, demonstrating the value of multi-omics approaches in addiction research.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57339-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57339-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57339-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().