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

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.