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Integration of molecular inflammatory interactome analyses reveal dynamics of circulating cytokines and extracellular vesicle long non-coding RNAs and mRNAs in heroin addicts during acute and protracted withdrawal

ABSTRACT: Heroin addiction and withdrawal influence multiple physiological functions including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the immune system function and molecular inflammatory interactome particularly the cytokines and RNA regulatory network in heroin addicts undergoing withdrawal compared healthy controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172306 | GEO | 2021/07/03

REPOSITORIES: GEO

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Determine the differential miRNA levels in plasma of heroin addicts

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Integration of Molecular Inflammatory Interactome Analyses Reveals Dynamics of Circulating Cytokines and Extracellular Vesicle Long Non-Coding RNAs and mRNAs in Heroin Addicts During Acute and Protracted Withdrawal.

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Integration of molecular inflammatory interactome analyses reveal dynamics of circulating cytokines and extracellular vesicle long non-coding RNAs and mRNAs in heroin addicts during acute and protracted withdrawal

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Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal.

Project description:BackgroundHeroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown.MethodsA total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal.ResultsAmong the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover.ConclusionsIn conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

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Determine the differential miRNA levels in plasma of heroin addicts

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Transcriptional effects of chronic heroin and methamphetamine treatment in the mouse striatum

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Project description:Noncoding RNAs, especially microRNAs (miRNAs) have been implicated in the regulation of neuronal functions, such as learning, cognition and memory formation. However, the particular miRNAs involved in drug-induced behavioral plasticity are largely unknown. Here we report a novel regulator, miR-218, that inhibits heroin-induced behavioral plasticity. Network propagation-based method revealed several miRNAs that play key roles in drug-addiction, among which, miR-218 was decreased in nucleus accumbens (NAc) after chronic exposure to heroin. Lentiviral overexpression of miR-218 in NAc could inhibit heroin-induced reinforcement in both conditioning place preference (CPP) test and heroin self-administration (SA) experiment. Luciferase activity assay indicated miR-218 could regulate neuroplasticity related genes and directly target Mecp2 3’UTR. Consistently, Mecp2-/y mice exhibited reduced heroin seeking behavior in CPP test. These data reveal a functional role of miR-218 and its target, Mecp2, in the regulation of heroin-induced behavioral plasticity.

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