Identification of post-generation effect of MDMA on the mouse brain by large-scale gene expression analysis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19914 | GEO | 2010/01/16
SECONDARY ACCESSION(S): PRJNA122097
REPOSITORIES: GEO
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Project description:The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier or venlafaxine (40 mg/kg) administration for 3 weeks continously. We also examined the possible interaction between the single dose MDMA treatment and the continous venlafaxine treatment described above. With the present study we tried to evaluate the effects of a single, neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA) and/or 3 weeks long venlafaxine (VLX) treatment in the dorsal raphe, frontal cortical or hippocampal neurons in Dark Agouti rats. For the analysis of MDMA long-term effects rats were treated once with 15 mg/kg MDMA i.p. in a volume of 1 ml/kg 3 weeks prior to sacrificing the animals. In the case of VLX, the animals were administered 40 mg/kg of the drug for 3 weeks via Alzet 2001 minipumps inserted under the skin of the rats. In the third group rats received the mentioned treatment protocols simultaneously. Vehicle and sham-operated controls were used for comparison. For microarray analysis all groups consisted of 8 animals. Every two randomly selected samples from the same brain regions were pooled resulting in 4 pooled samples per region and treatment. From the total 48 pooled samples 2 were excluded because of quality control reasons. For RNA extraction Trizol reagent was used and microarray analysis was done by Service XS (Netherlands) according to Illumina protocols (San Diego, CA, USA). Results were validated with Fluidigm GEx (San Francisco, CA, USA) arrays using TaqMan Gene Expression (Carlsbad, CA, USA) assays. In this study no replicates were used.
2013-06-01 | E-GEOD-47541 | biostudies-arrayexpress
Project description:The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier or venlafaxine (40 mg/kg) administration for 3 weeks continously. We also examined the possible interaction between the single dose MDMA treatment and the continous venlafaxine treatment described above.
2013-06-01 | GSE47541 | GEO
Project description:Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and long-lasting antidepressant-like and anxiolytic effects. The mechanism of action underlying these effects is not yet fully understood. This study investigated the downstream gene expression changes and signaling pathways affected by methylone in key brain areas linked to PTSD and MDD. It also sought to determine whether neuroplasticity-related genes were involved. We compared effects of methylone with MDMA to explore similarities and differences in their brain effects because MDMA-assisted psychotherapy has recently shown benefit in clinical trials for PTSD and methylone is a structural analog of MDMA. Methods: We used RNA sequencing (RNA-seq) to probe drug-induced gene expression changes in the amygdala and frontal cortex, two brain areas responsible for emotional learning that are affected by PTSD and MDD. Rats were treated with methylone or MDMA (both 10 mg/kg, IP), and their responses were compared with controls. Results: RNA-seq results revealed significant regulation of myelin-related genes in the amygdala, confirmed by immunohistochemistry. In the frontal cortex, methylone significantly upregulated genes implicated in neuroplasticity. Conclusions: Results suggest that (1) methylone is a rapid-acting neuroplastogen that affects key brain substrates for PTSD and MDD and that (2) methylone appears to exhibit higher specificity and fewer off-target effects than MDMA. Together, these results are consistent with the reported clinical experiences of methylone and MDMA and bolster the potential use of methylone in the treatment of PTSD and, potentially, other neuropsychiatric disorders.
2024-01-18 | GSE253280 | GEO
Project description:In this study, we performed miRNA profiling of nucleus accumbens (NAc) and ventral tegmental area (VTA) in MDMA users and control postmortem human brains, which were obtained from Council of Forensic Medicine (Istanbul). According to the microarray analysis of significantly differentially expressed miR-1202 and miR-7975 were selected for further validation using quantitative reverse-transcription PCR (qRT-PCR). qRT-PCR analysis demonstrated that the expression level of miR-7975 was significantly lower in 30 VTA region of MDMA samples compared to 30 control samples. Another significantly deregulated miR-1202 was down-regulated in 30 NAc region of MDMA samples in comparison to 30 control samples. To the best of our knowledge, this is the first study demonstrating that changes in miRNA expression levels are associated with postmortem MDMA users’ brains. Alteration of these miRNAs can serve as novel biomarkers for prediction of MDMA addiction. Our findings suggest that certain differentially expressed miRNAs in MDMA seeking behavior can be used as diagnostics and therapeutic markers.
2020-03-24 | GSE104315 | GEO
Project description:MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA’s acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy (CM). MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10d or 35d MDMA , or daily 10d MDMA followed by 25d saline washout (10+25d). MDMA treatment (10d) caused differentially gene expression (p<0.05, fold change >1.5), with 752 genes 558 genes following 35d MDMA, and 113 genes following 10d treatment +25d washout. Changes in MAPK and circadian rhythm gene expression were identified following 10d administration. After 35d, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) remained differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was 71% at 10d, 68% at 35d, and 91% at 10+25d. Differential gene expression that corresponded directly with DNA methylation changes occurred in 22% of genes at 10d, 17% at 35d, and 48% at 10d+25d washout. MDMA treatment resulted in epigenetic changes in cardiac DNA methylation. Hypermethylation was the predominant effect. MDMA induced gene expression of key elements of circadian rhythm regulatory genes and suggest a fundamental mechanism for MDMA dysfunction in the heart. This study addresses how MDMA (ecstasy) affects cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation.
2015-12-11 | GSE68175 | GEO
Project description:MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA’s acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy (CM). MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10d or 35d MDMA , or daily 10d MDMA followed by 25d saline washout (10+25d). MDMA treatment (10d) caused differentially gene expression (p<0.05, fold change >1.5), with 752 genes 558 genes following 35d MDMA, and 113 genes following 10d treatment +25d washout. Changes in MAPK and circadian rhythm gene expression were identified following 10d administration. After 35d, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) remained differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was 71% at 10d, 68% at 35d, and 91% at 10+25d. Differential gene expression that corresponded directly with DNA methylation changes occurred in 22% of genes at 10d, 17% at 35d, and 48% at 10d+25d washout. MDMA treatment resulted in epigenetic changes in cardiac DNA methylation. Hypermethylation was the predominant effect. MDMA induced gene expression of key elements of circadian rhythm regulatory genes and suggest a fundamental mechanism for MDMA dysfunction in the heart. This study addresses how MDMA (ecstasy) affects cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation.
2015-12-11 | GSE68199 | GEO
Project description:MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMAâs acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy (CM). MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10d or 35d MDMA , or daily 10d MDMA followed by 25d saline washout (10+25d). MDMA treatment (10d) caused differentially gene expression (p<0.05, fold change >1.5), with 752 genes 558 genes following 35d MDMA, and 113 genes following 10d treatment +25d washout. Changes in MAPK and circadian rhythm gene expression were identified following 10d administration. After 35d, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) remained differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was 71% at 10d, 68% at 35d, and 91% at 10+25d. Differential gene expression that corresponded directly with DNA methylation changes occurred in 22% of genes at 10d, 17% at 35d, and 48% at 10d+25d washout. MDMA treatment resulted in epigenetic changes in cardiac DNA methylation. Hypermethylation was the predominant effect. MDMA induced gene expression of key elements of circadian rhythm regulatory genes and suggest a fundamental mechanism for MDMA dysfunction in the heart. This study addresses how MDMA (ecstasy) affects cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation. Each sample was fluorescently labeled and hybridized to Roche Nimblegen 2.1M Deluxe Promoter Arrays.
2015-12-11 | E-GEOD-68199 | biostudies-arrayexpress
Project description:MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMAâs acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy (CM). MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10d or 35d MDMA , or daily 10d MDMA followed by 25d saline washout (10+25d). MDMA treatment (10d) caused differentially gene expression (p<0.05, fold change >1.5), with 752 genes 558 genes following 35d MDMA, and 113 genes following 10d treatment +25d washout. Changes in MAPK and circadian rhythm gene expression were identified following 10d administration. After 35d, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) remained differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was 71% at 10d, 68% at 35d, and 91% at 10+25d. Differential gene expression that corresponded directly with DNA methylation changes occurred in 22% of genes at 10d, 17% at 35d, and 48% at 10d+25d washout. MDMA treatment resulted in epigenetic changes in cardiac DNA methylation. Hypermethylation was the predominant effect. MDMA induced gene expression of key elements of circadian rhythm regulatory genes and suggest a fundamental mechanism for MDMA dysfunction in the heart. This study addresses how MDMA (ecstasy) affects cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation. Each sample was fluorescently labeled and hybridized to Roche Nimblegen 12X135kb MM9 Gene Expression Arrays.
2015-12-11 | E-GEOD-68175 | biostudies-arrayexpress
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2015-12-31 | GSE61301 | GEO
Project description:Epicatechin (EC) is a well-known dietary polyphenol and widely found in various foods, e.g., apple, cocoa, green tea, wine, etc. Its consumption has been associated with attenuation of some chronic diseases. After ingestion of EC, a large portion is passed into the large intestinal lumen where it is extensively degraded into various microbial metabolites. One of the major EC microbial metabolites is 5-(3’,4’-dihydroxyphenyl)-γ-valerolactone (3,4-diHPV). The protein expression profiles of EC or 3,4-diHPV treated Caco-2 and Hepa1c1c7 cells were studied with the help of label-free quantitative proteomics. Compared to the parent compound EC, 3,4-diHPV was able to induce upregulations of more Nrf2-related proteins in both cell lines, and the number of significant differentially expressed proteins (DEPs) induced by 3,4-diHPV in Hepa1c1c7 cells was much higher than the respective EC treatment.
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