Hippocampal single-cell RNA Atlas of chronic methamphetamine abuse-induced cognitive decline in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE252939 | GEO | 2025/09/30
REPOSITORIES: GEO
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Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain
2011-11-15 | E-GEOD-33707 | biostudies-arrayexpress
Project description:Hippocampal single-cell RNA Atlas of chronic methamphetamine abuse-induced cognitive decline in mice
| PRJNA1063271 | ENA
Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations.
2011-11-15 | GSE33707 | GEO
Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall “omic” response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals.
2010-10-31 | GSE16198 | GEO
Project description:To investigate the effects of methamphetamine on immune cells, we established three methamphetamine abuse immune cell models. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different immune cell models.
2022-07-06 | GSE201007 | GEO
Project description:Methamphetamine can trigger dopamine releasing in human brain, now used as abuse drug. Some studies have shown that specific genes and proteins responded to, methamphetamine, but little is known about the overall omic response of organisms to this illicit substance. Here we demonstrate that Drosophila melanogaster has the potential to give us significant insights into evolutionarily conserved responses to methamphetamine. We performed metabolome, proteome, and transciptome profiling with Drosophila treated with methamphetamine. The proteomic profiling revealed responses associated with known physiological problems that occur with methamphetamine usage in mammals. The metabolomic result showed that the metabolite trehalose was decreased significantly after methamphetamine exposure, suggesting an oxidative stress response to this drug. Many of the differential transcribed genes, including detoxification enzymes, had the potential transcription factor-binding motif YY1 associated with their upstream regulatory regions. YY1 is known to be responsive to amphetamines in mammals. For each sample, 20 virgin male flies were used to extract the mRNA. Three replicates were produced for each treatments. Two treatments were produced (control VS 0.6% 24 h meth-fed).
2010-10-30 | E-GEOD-16198 | biostudies-arrayexpress
Project description:Both drugs abuse and HIV infection continue to affect many indiviiduals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse such as the psychostimulant methamphetamine. In order to determine the interaction of HIV and methamphetamine we isolated microglia and macrophages from the brains of SIV-infected rhesus monkeys treated with methamphetamine and from SIV-infected monkeys who did not receive methamphetamine. Cells were subjected to single cell RNA sequencing and results analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of cells were infected by SIV. In addition, genes encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of cells from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.
2020-12-01 | GSE160384 | GEO
Project description:In this study, we have created a mouse model of methamphetamine cardiomyopathy that reproduces the chronic, progressive dosing commonly encountered in addicted subjects. We gradually increased the quantity of methamphetamine given to C57Bl/6 mice from 5 to 40 mg/kg over five months. At the fifth month, heart weight was increased, echocardiograms showed a dilated cardiomyopathy and survival was lower in males, with less effect in females. Interestingly, these findings correspond to previous observations in human patients, suggesting greater male susceptibility to the effects of methamphetamine on the heart.Transcriptional analysis showed changes in genes dysregulated in previous methamphetamine neurological studies as well as many that likely play a role in cardiac response to this toxic stress. We expect that a deeper understanding of the molecular biology of methamphetamine exposure in the heart will provide insights into the mechanism of cardiomyopathy in addicts and potential routes to more effective treatment.
2018-09-01 | GSE109790 | GEO
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.
2021-12-15 | GSE190800 | GEO
Project description:In summary, we characterized genomic signatures of response to drugs of abuse and we found positive correlations between the drug-induced expression and various behavioral effects. These signatures are formed by two dynamically inducible transcriptional networks: (1) CREB/SRF-dependent gene pattern that appears to be related to drug-induced neuronal activity, (2) the pattern of genes controlled at least in part via release of glucocorticoids and androgens that are associated with rewarding and harmful drug effects. The discovery of co-expressed networks of genes allowed for the identification of master-switch controlling factors involved in molecular response to the drugs. Finally, using the pharmacological tools we were able to dissect and inhibit particular gene expression patterns from genomic profile. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Addiction, Drugs of abuse, Time-course, Immediate Early Genes, Glucocorticoid receptor dependent genes, Cocaine, Heroin, Nicotine, Ethanol, Morphine, Methamphetamine The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Six the most addictive and harming drugs of abuse (morphine 20 mg/kg, heroin 10 mg/kg, ethanol 2 g/kg, nicotine 1 mg/kg, methamphetamine 2 mg/kg or cocaine 25 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as rewarding in mice and further tested in our laboratory. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naïve animals were prepared for each time point. Design of the experiment assumed pooling of two animals per each array and using of three independent arrays per group. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2010-04-14 | E-GEOD-15774 | biostudies-arrayexpress