Microrna-Mrna Networks Are Dysregulated in Opioid Use Disorder Postmortem Brain: Further Evidence for Opioid-Induced Neurovascular Alterations

Authors

Sandra L Grimm
Emily F Mendez
Laura Stertz
Thomas D Meyer
Gabriel R Fries
Tanmay Gandhi
Rupa Kanchi
Sudhakar Selvaraj
Antonio L Teixeira
Thomas R Kosten
Preethi Gunaratne
Cristian Coarfa
Consuelo Walss-Bass

Publication Date

1-12-2023

Journal

Frontiers in Psychiatry

Abstract

INTRODUCTION: To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.

METHODS: Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues.

RESULTS: miRNA-mRNA network analysis showed that even though miRNAs identified in BA9 and blood were fairly distinct, their target genes and corresponding enriched pathways overlapped strongly. Among the dominant enriched biological processes were tissue development and morphogenesis, and MAPK signaling pathways. These findings point to robust, redundant, and systemic opioid-induced miRNA dysregulation with a potential functional impact on transcriptomic changes. Further, using correlation network analysis, we identified cell-type specific miRNA targets, specifically in astrocytes, neurons, and endothelial cells, associated with OUD transcriptomic dysregulation. Finally, leveraging a collection of control brain transcriptomes from the Genotype-Tissue Expression (GTEx) project, we identified a correlation of OUD miRNA targets with TGF beta, hypoxia, angiogenesis, coagulation, immune system, and inflammatory pathways.

DISCUSSION: These findings support previous reports of neurovascular and immune system alterations as a consequence of opioid abuse and shed new light on miRNA network regulators of cellular response to opioid drugs.

Keywords

opioid use disorder, microRNA, brain, network analysis, neurovascular, blood, prefrontal cortex

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Supplementary Materials

PMID: 36713930