Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA350673 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2017-03-08 | GSE89202 | GEO
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.
2009-01-29 | E-GEOD-13166 | biostudies-arrayexpress
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
2009-01-30 | GSE13166 | GEO
Project description:Opioid abuse produces enduring associations between the drug euphoria and features of the drug-taking experience, and these powerful associations can trigger relapse in individuals recovering from opioid use disorder. We show here that the epigenetic enzyme, histone deacetylase 5 (HDAC5), functions in the nucleus accumbens (NAc) during active heroin use to limit future relapse-like behavior. Moreover, enhancing HDAC5 function in NAc dramatically suppresses context-associated and reinstated heroin seeking behaviors, but it does not impact sucrose seeking. We also find that HDAC5 functions within dopamine D1 receptor-expressing medium spiny neurons (MSNs) to suppress cue-induced heroin seeking, but within dopamine D2 receptor-expressing MSNs to suppress drug-primed heroin seeking. Using cell type-specific transcriptomics analysis, we found that HDAC5 reduces expression of numerous genes linked to ion transport, and it decreases intrinsic excitability of NAc MSNs, suggesting that HDAC5 limits relapse vulnerability by suppressing NAc MSN firing rates during active heroin use. We used microarrays to define genes differentially expressed in the presence or absence of AAV2-DIO-HDAC5-3SA in both D1 and D2 cell-types derived from Nucleus accumbens following vTRAP.
2023-03-01 | GSE199985 | GEO
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.
2022-02-20 | GSE169628 | GEO
Project description: Not available
| S-EPMC9277659 | biostudies-literature
Project description:The invasion front of oral squamous cell carcinoma (OSCC) harbors the most aggressive cells of the tumor and is critical for cancer invasion and metastasis. MicroRNAs (miRNAs) play an important role in regulating OSCC invasion. In this study, we modeled the OSCC invasion front on a microfluidic chip and investigated differences in miRNA profiles between cells in the invasion front and those in the tumor mass by small RNA sequencing and bioinformatic analysis. We found that miR-218-5p was downregulated in invasion front cells; a luciferase reporter assay confirmed that cluster of differentiation (CD)44 was a direct target of miR-218-5p. Inhibiting miR-218-5p in invasion front cells activated CD44- Rho-associated protein kinase (ROCK) signaling and promoted cell invasion by inducing cytoskeletal reorganization. These findings indicate that miR-218-5p negatively regulates OSCC invasiveness by targeting the CD44–ROCK pathway and may be a useful therapeutic target for OSCC. Moreover, our method of modeling and isolating invasion front cells using a microfluidic chip is a time-saving alternative to in vivo models.
2018-05-21 | GSE107243 | GEO
Project description: Not available
| S-EPMC7145424 | biostudies-literature
Project description: Not available
| S-EPMC7161169 | biostudies-literature
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
2016-08-18 | GSE81418 | GEO