Proteomics

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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]

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