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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: 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

PROVIDER: PRJNA722883 | ENA |

REPOSITORIES: ENA

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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

Project description: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.

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Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

Project description:Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder (SUD). Recent data from our laboratory indicate that aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly to cocaine-seeking behavior following prolonged periods of abstinence. It remained unclear, however, whether this modification is important for relapse vulnerability in the context of other drugs of abuse, such as opioids. Here, we showed that H3Q5dop plays a critical role in heroin-mediated transcriptional plasticity in midbrain. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. By attenuating H3Q5dop during abstinence, we both altered gene expression programs associated with heroin withdrawal and reduced heroin-primed reinstatement behavior. These findings thus establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in opioid-induced plasticity in VTA.

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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.

Project description: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 molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.

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Project description:Several studies have investigated changes induced by drug exposure, but few reports have described changes that persist following relapse. In the present study, genome-wide analysis of gene expression was conducted in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. The medial prefrontal cortex (mPFC) is important in mediating goal-directed behavior and also was the target of this analysis. Rats were trained to self-administer heroin (0.06 mg/0.2 ml infusion) during 3 hour daily sessions for 14 days. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session. The extinction session occurred either 1 day or 14 days following the final self-administration session. Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 day abstinent period. Whole genome analysis was performed and selected results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p<0.02) following 14 days of abstinence and the 90-minute extinction session, and seven of the genes on which RT-qPCR was performed were confirmed (BDNF, Calb1, Dusp5, Dusp6, EGR1, NPY, RGS2). Ontological analysis indicates that several of the genes with changed expression in this study are important for behavior and learning. The importance of drug-seeking behavior and memory of previous sessions of drug-taking suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse. Keywords: heroin self-administration cRNA from 6 rats that self-administered heroin was compared to cRNA from 5 rats that received yoked infusions of saline.

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Determine the differential miRNA levels in plasma of heroin addicts

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Project description:GWAS of Heroin Dependence

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