Dataset Information

Uncovering diurnal rhythm disruptions of synaptic proteome signaling in prefrontal cortex and nucleus accumbens associated with opioid use disorder

ABSTRACT: This article presents a study that examines the proteomic alterations associated with opioid use disorder (OUD) in the human brain. The study investigates the interplay between pro-inflammatory signaling, extracellular matrix (ECM) remodeling, and synaptic plasticity in the corticostriatal circuitry associated with OUD. The findings reveal differential alterations in the synaptic proteomes across the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC), indicating that changes in certain synaptic subtypes are unique to each brain region. The proteomic alterations associated with OUD in DLPFC are mainly in glutamatergic, serotonergic, dopaminergic, and oxytocin signaling, while altered adrenergic signaling is enriched in NAc. The study also identifies alterations in proteins involved in circadian entrainment specifically in synaptic enrichments in both DLPFC and NAc of OUD subjects. These findings provide new evidence linking disrupted molecular rhythms in the regulation of distinct synaptic subtypes altered by opioids.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Matthew MacDonald

LAB HEAD: Matthew L MacDonald

PROVIDER: PXD041333 | Pride | 2023-10-25

REPOSITORIES: Pride

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Publications

Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.

Puig Stephanie S Xue Xiangning X Salisbury Ryan R Shelton Micah A MA Kim Sam-Moon SM Hildebrand Mariah A MA Glausier Jill R JR Freyberg Zachary Z Tseng George C GC Yocum Anastasia K AK Lewis David A DA Seney Marianne L ML MacDonald Matthew L ML Logan Ryan W RW

Molecular psychiatry 20230906 11

Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions. Understanding the neurobiological underpinnings of circadian rhythms and opioid use disorder (OUD) may prove valuable for developing new treatments for opioid addiction. Previous work indicated molecular rhythm disruptions in the human brain associated with OUD, highlighting synaptic alterations in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc)-key bra ...[more]

PMID: 37674018

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Project description:Molecular basis of transition to addiction in vulnerable individuals is largely unknown. We hypothesized that human susceptibility genes can be identified on the basis of conserved molecular mechanisms in rodent brains. We used a short-term cocaine-dependent conditioned place preference (CPP) to identify genetic hallmarks of early steps of reward memory in basal ganglia including accumbens nucleus (NAc), globus pallidus (GP) and subthalamic nucleus (STN). Using genome-wide microarray analysis and CPP as a quantitative trait, we found that synaptic plasticity-related genes are deregulated in these three structures. A significant enrichment in bona fide transcripts involved in dendritic spine local translation was evidenced. mGluR5 is transcriptionally deregulated in Acc and GP of cocaine-treated animals. Grin3a that encodes a NMDA receptor subunit involved in Ca++ permeability is deregulated in NAc. Furthermore, Orexin/Hcrt transcript level is decreased in STN, a region known to be involved in discriminating addictive drugs and natural rewards. We also found that mGluR5 and Grin3a expression deregulation is sufficient to induce changes in synaptic plasticity-related genes. Altogether, these results suggest that a combined deregulation of mGluR5 and Grin3A pathway in NAc, mGluR5 in GP and orexin system in STN may generate an incentive memory contrasted between addictive drugs and natural rewards. Such pathways may include clusters of genes that are potential susceptibility genes for transition to addiction. Agilent Whole Mouse Genome oligomicroarrays (GEO accession no. GPL4134, Agilent Technologies, Palo Alto, CA) were used. They contain 60-mer DNA probes synthesized in situ in a 44k format. Four independent (globus pallidus from mouse treated with cocaine and having a high score of conditioned place preference compared to globus pallidus from mouse treated with saline solution) measurements were carried out for each group of biological conditions using exchanged dye-labeled RNA targets (i.e., Cy3 and Cy5 dyeswapping experiments).

Dataset Information

Uncovering diurnal rhythm disruptions of synaptic proteome signaling in prefrontal cortex and nucleus accumbens associated with opioid use disorder

Publications

Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.

Similar Datasets

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