Cocaine Induces Differential Circular RNAs Expression in Striatum
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ABSTRACT:
PROVIDER: PRJNA445834 | ENA |
REPOSITORIES: ENA
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Project description:Circular RNA (circRNA) has recently emerged as a novel type of endogenous non-coding RNA. It plays natural microRNA sponge effect that represses the activity of corresponding miRNAs by binding with them, thus regulating gene expression. Recent studies demonstrate that circRNAs are significantly enriched in the brain and a disproportionate fraction of them is derived from host genes that code for synaptic proteins. In addition, studies have shown that microRNAs are involved in synaptic plasticity, memory formation and cocaine addiction. However, the role of circRNAs in cocaine reward is largely unknown. This study aimed to identify the expression profile of circRNAs in the striatum of mice after cocaine self-administration by using circRNA microarray analysis.
2020-04-01 | GSE112370 | GEO
Project description:Circular RNA (circRNA), a novel type of endogenous non-coding RNA, plays natural miRNA sponge effect that represses the activities of corresponding miRNAs through binding with them, thus modulating transcriptional expression of genes. Recent studies indicate that circRNAs are significantly enriched in the brain and some of them are derived from synaptic protein-coding genes. In addition, miRNAs are involved in synaptic plasticity, memory formation, and cocaine addiction. However, the role of circRNAs in cocaine reward is unclear. This study aimed to investigate the expression profile of striatal circRNAs in the mice after cocaine self-administration. By using circRNA microarray analysis, we observed that 90 striatal circRNAs were differentially expressed in cocaine self-administering mice, of which 18 circRNAs were up-regulated and 72 down-regulated. Six circRNAs were selected randomly for validation by using quantitative reverse transcription-PCR, and their expression levels showed consistency with microarray analysis. We backward predicted the circRNAs and their binding sites of miRNAs associated with neuroplasticity. In functional validation test, mmu_circRNA_002381 may modulate the transcription of certain genes associated with neuroplasticity, such as limk1 and bdnf. Taken together, circRNAs may participate in cocaine behavioral effect via interacting with miRNAs. Our findings reveal a potential role of circRNAs in cocaine effect.
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Project description:Comparison of gene expression in the dorsal striatum of rats after chronic binge or acute binge cocaine injections or saline treatment
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Project description:Cocaine-dependent genome-wide effects were analyzed, total RNAs were extracted from ventral striatum tissue punches and processed for RNA-seq analyses.
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Project description:<p>This project characterizes DNA methylation and gene expression changes that occur in the human brain, specifically in neurons from the rostral striatum. Major advances from NIDA funded initiatives for noninvasive neuroimaging studies have made it possible to study neuroanatomical, neurochemical and functional changes in the human brain that contribute to the vulnerability to abuse drugs, together with the neurotoxic consequences of years of drug misuse. Animal models have been developed to explain the fundamental behavioral and biological mechanisms of addiction, including reward, tolerance and dependence. From these studies, we learned that cocaine abuse not only alters the epigenetic status of genes, but also induces particular epigenetic modifications depending on the frequency of the drug's administration. Certain genes are switched on by infrequent (short-term exposure) administration, while others are switched on only after chronic administration (addiction/dependence). Animal studies have also suggested that cocaine-seeking habits modeling chronic cocaine addiction in humans depend upon dopamine-dependent serial connectivity linking the ventral (nucleus accumbens) with the dorsal striatum (caudate nucleus). The primary goal of this study is to identify DNA methylation and gene expression changes that occur in the transition from recreational cocaine use to cocaine addiction. High throughput sequencing studies were designed to investigate unique postmortem human brain specimens from individuals that met criteria for cocaine dependence, as compared to unaffected age-matched controls.</p> <p>Brain biospecimens were available from the University of Miami Brain Endowment BankTM, from a collection of phenotypically well-characterized postmortem tissues sampled from chronic cocaine abusers that came to autopsy. This biobank of postmortem brain specimens and annotated genomic data serve as a research resource to support NIDA's scientific mission.</p>
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Project description:Drug abuse is a major concern with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors, and have profound effects on cellular signaling. Thus, targeting these dynamic interactions represents a novel therapeutic modality. Our previous studies have indicated increased HS proteoglycan syndecan-3 and identified HS as a resilience factor for cocaine abuse. Here, we utilized mass spectrometry-based glycomics and proteomics to understand the effects of cocaine (C) and methamphetamine (M) on HS, CS, and proteins from two brain regions: lateral hypothalamus (LH) and striatum (ST) from mice. We observed significant differences in HS and CS total abundances and percent sulfate contents and reduction in CS 4-O-sulfation, and increase in CS 6-O-sulfation for drug-treated (C and M) vs. saline samples. The proteomics data revealed a number of aberrant proteins in drug-treated vs. saline samples, including MYPR, KCC2A, SYN2, TENR, CALX, ANXA7, HDGF, NCAN, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, our study shows for the first time the novel relationship of HS, CS, and associated proteins with the drug abuse, and shed light on, the underlying neurobiological mechanism of drug dependence and novel therapeutic options.
2024-09-04 | PXD038576 | Pride