Project description:Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain’s reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that result from drug use. Therefore, using large scale proteomics studies we aim to identify global protein expression changes within the dorsal striatum, a key brain region involved in the modulation of addiction. We performed LC-MS/MS analyses on rat striatal synaptosomes following 30 days of methamphetamine self-administration (2 hours/day) and 14 days abstinence. We identified a total of 84 differentially-expressed proteins with known roles in neuroprotection, neuroplasticity, cell cytoskeleton, energy regulation and synaptic vesicles. We identify significant expression changes in stress-induced phosphoprotein and protein Tppp, which have not previously been associated with addiction. In addition, we confirm the role of amphiphysin and phosphatidylethanolamine binding protein in addiction. This approach has provided new insight into the effects of methamphetamine self-administration on synaptic protein expression in a key brain region associated with addiction, showing a large set of differentially-expressed proteins that persist into abstinence.
Project description:Using ssRNA-seq, we examined the alteration of transcription profiles in the nucleus accumbens of methamphetamine-sensitized mice. Methamphetamine was a commonly abused psychostimulant. Repeated exposure to methamphetamine elicited long-lasting cellular and molecular changes, including the aberrant expression of coding and non-coding RNAs, which may involve in methamphetamine-induced locomotor sensitization and addiction.
Project description:Methamphetamine addiction is mimicked in rats that self-administer the drug and accelerate their intake when given long access to it. Self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Here, we studied transcriptional consequences of methamphetamine SA and repeated foot-shocks in rat brain.
Project description:Methamphetamine addiction is mimicked in rats that self-administer the drug and accelerate their intake when given long access to it. Self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Here, we studied transcriptional consequences of methamphetamine SA and repeated foot-shocks in rat brain.
Project description:Genome wide DNA methylation profiling of normal and methamphetamine (MA) abusers with different addiction susceptibility. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles in peripheral blood lymphocytes (PBLs). Samples included 8 health controls, 8 high MA addiction susceptibility (HMAS) abusers, and 8 high MA addiction susceptibility (LMAS) abusers.
Project description:Using microRNA-Seq, we examined the alteration of microRNA expression profiles in the nucleus accumbens of methamphetamine-sensitized and saline-control mice. Nucleus accumbens lysate from eight mice of each group were pooled as one sample. Two RNA samples from each group were prepared and were then processed to generate small RNA libraries, which were sequenced on the Illumina Hiseq 2000. The aberrant expression of microRNAs identified in this study may involve in METH-induced locomotor sensitization and addiction.
Project description:<p><strong>BACKGROUND:</strong> Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) addicts, the role of the microbiome plays in this process is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH addicts. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH addicts and 105 healthy controls (CTL) undergoing detoxification at the detoxification center in Shandong, China. In addition, the untargeted metabolomic profiling was conducted based on 220 samples (170 METH addicts and 50 CTL) to identify the biomarkers and build classifiers for both oral microbiota and metabolites.</p><p><strong>RESULTS:</strong> Compared to the CTL group, alpha diversity was reduced in the group of METH addicts, with significant differences in the microbiota and changes in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., <em>Peptostreptococcus</em>, <em>Gemella</em>, <em>Campylobacter</em> and <em>Aggregatibacter</em>, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. And, it was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. In addition, microbial prediction models were more effective than metabolite-based prediction models in identifying METH addiction.</p><p><strong>CONCLUSIONS:</strong> Our study identified the potential functional connections between the oral microbiome and metabolic profile of METH addicts, providing novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.</p>
Project description:As one of the most commonly abused substances in the world, methamphetamine (METH) addiction and use disorders cause a huge burden for society. The prefrontal cortex (PFC) is a vital brain region associated with emotion and cognitive behaviors that is also intimately involved in the neurocircuitry of addiction syndrome. Bulk RNA-seq has revealed the effects of METH on disease-related genes alterations in the mouse PFC; however, the roles of different cell types are still unknown. We performed single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of 20,698 nuclei isolated from the PFC of chronic METH-treated and control mice.
Project description:Due to the complexity and diversity of the cellular changes, our understanding of the exact molecular and cellular mechanisms underpinning behavioral sensitization remains incomplete. Therefore, the present study explored the single-cell transcriptional changes in the orbitofrontal cortex (OFC) — a region implicated in decision-making and reward-related behaviors15,16— in a rodent model of methamphetamine-induced sensitization. Our study provides insights into the molecular mechanisms cells associated with the development of drug addiction.
