Psychotropic drug-induced gene expression alterations in mouse striatum I
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE48951 | GEO | 2013/07/18
SECONDARY ACCESSION(S): PRJNA212394
REPOSITORIES: GEO
Similar Datasets
Project description:To identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found. The additional data-sets are available at GEOX1 and GEOX2.
2013-07-18 | GSE48954 | GEO
Project description:To identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found. The additional data-sets are available at GEOX1 and GEOX2. The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Three antidepressants (bupropion 20 mg/kg, tranylcypromine 20 mg/kg, mianserin 20 mg/kg, i.p.), three anxiolytics (diazepam 5 mg/kg, buspirone 10 mg/kg, hydroxyzine 10 mg/kg, i.p.), and three antipsychotics (clozapine 3 mg/kg, risperidone 0.5 mg/kg, haloperidol 1 mg/kg) were selected for the comparison. Drug doses were previously reported as effective 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 or tween (1% Tween 80) 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.
2013-07-18 | E-GEOD-48954 | biostudies-arrayexpress
Project description:To identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found. The additional data-sets are available at GEOX1 and GEOX2. The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Three antidepressants (imipramine 10 mg/kg, fluoxetine 20 mg/kg and tianeptine 20 mg/kg, i.p.) were selected for the comparison. Drug doses were previously reported as effective 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.
2013-07-18 | E-GEOD-48951 | biostudies-arrayexpress
Project description:Substance use disorders (SUDs) are associated with disruptions in sleep and circadian rhythms that persist during abstinence and may contribute to relapse risk. Repeated use of substances such as psychostimulants and opioids may lead to significant alterations in molecular rhythms in the nucleus accumbens (NAc), a brain region central to reward and motivation. Previous studies have identified rhythm alterations in the transcriptome of the NAc and other brain regions following the administration of psychostimulants or opioids. However, little is known about the impact of substance use on the diurnal rhythms of the proteome in the NAc. We used liquid chromatography coupled to tandem mass spectrometry-based (LC-MS/MS) quantitative proteomics, along with a data-independent acquisition (DIA) analysis pipeline, to investigate the effects of cocaine or morphine administration on diurnal rhythms of proteome in the mouse NAc. Overall, our data reveals cocaine and morphine differentially alters diurnal rhythms of the proteome in the NAc, with largely independent differentially expressed proteins dependent on time-of-day. Pathways enriched from cocaine altered protein rhythms were primarily associated with glucocorticoid signaling and metabolism, whereas morphine was associated with neuroinflammation. Collectively, these findings are the first to characterize the diurnal regulation of the NAc proteome and demonstrate a novel relationship between phase-dependent regulation of protein expression and the differential effects of cocaine and morphine on the NAc proteome.
2023-07-20 | PXD042043 | Pride
Project description:Abstract: Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces life-long pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic β cells permanently reduces their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production. Synopsis: The abuse of illicit drugs is a major societal problem, including their continued use during pregnancy. Even though harmful effects of commonly-used psychostimulants to the unborn fetus have been postulated, if and how maternal exposure to illicit psychostimulants during pregnancy could reprogram the fetal pancreas and limit glucose metabolism and tolerance for life in affected offspring remain unknown. Here, we combine human and mouse data to outline the sex-specific epigenetic deregulation of serotonin signaling-related gene regulatory networks, which leads to reduced insulin production postnatally. • As little as episodic intrauterine psychostimulant exposure is sufficient to permanently limit beta cell function in postnatal female rather than mouse male offspring. • The serotonin transporter, rather than the dopamine transporter, is identified as a molecular target of psychostimulants in fetal beta cells and in beta cell-like cellular models. • Psychostimulants adversely affect protein serotonylation in beta-cell models. • Altered DNA methylation and accessibility link the life-long deregulation of transcription factors and genes shaping serotonin signaling with reduced functionality in beta cells.
2019-11-07 | GSE140072 | GEO
Project description:Substance abuse and addiction represent a major public health problem that impacts multiple dimensions of society, including healthcare, economy, and workforce. In 2021, over 100,000 drug overdose deaths have been reported in the US with an alarming increase in fatalities related to opioids and psychostimulants. Understanding of the fundamental gene regulatory mechanisms underlying addiction and related behaviors could facilitate more effective treatments. To explore how repeated drug exposure alters gene regulatory networks in the brain, we combined capped small (cs)RNA-seq, which accurately captures nascent-like initiating transcripts from total RNA, with Hi-C and single nuclei (sn)ATAC-seq. We profiled initiating transcripts in two addiction-related brain regions, the prefrontal cortex (PFC) and the nucleus accumbens (NAc), from rats that were never exposed to drugs or were subjected to prolonged abstinence after oxycodone or cocaine intravenous self-administration (IVSA). Interrogating in total over 100,000 active transcription start regions (TSRs) revealed that most TSRs had hallmarks of bona-fide enhancers and highlighted the KLF/SP1, RFX and AP1 transcription factors families as central to establishing brain-specific gene regulatory programs. Analysis of rats with addiction-like behaviors versus controls, identified addiction-associated repression of transcription at regulatory enhancers recognized by nuclear receptor subfamily 3 group C (NR3C) factors, which include glucocorticoid receptors. Cell-type deconvolution analysis using snATAC-seq uncovered a potential role of glial cells in driving the gene regulatory programs associated with addiction-related phenotypes. These findings highlight the power of advanced transcriptomics methods to provide insight into how addiction perturbs gene regulatory programs in the brain.
2022-05-11 | GSE193757 | GEO
Project description:Drug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence.
2013-06-27 | GSE43748 | GEO
Project description:HIV transmission involves the adhesion to and migration of infected cells, including monocytes across biological barriers comprising extracellular matrix components. Recently, semen exosomes (SE) from HIV uninfected (HIV-) and HIV infected (HIV+) subjects were shown to contain molecules that were adhesive to Jurkat T cells. Since monocyte trafficking across various biological barriers are intensified by HIV and/or illicit substances, such as cocaine, we sought to understand how SE from HIV infected subjects’ comorbid with illicit drug abuse influence monocyte gene expression and behavior. Therefore, a model of U937 monocyte adhesion on collagen-coated surface in the presence and absence of SE from various clinical (HIV-Drug-, HIV-Drug+, HIV+Drug-, and HIV+Drug+) groups was developed. Using this system, we demonstrate by Microarray analysis that SE from different clinical groups reprogramed gene expression profile of monocytes cultured atop collagen. In line with altered gene expression is increased adhesion of monocytes to collagen following treatment with SE from all clinical groups compared to vehicle. Interestingly, SE from HIV+ subjects’ comorbid with drug abuse potentiated monocyte adhesion to collagen. Mechanistically, SE-Drug and SE-HIV altered monocyte shape, induced actin cytoskeleton reorganization, formation of membrane ruffles and lamellipodia-like structures, as well as focal-adhesion contacts. The cytoskeletal reorganization induced by SE-Drug is associated with impairment of cell motility, while SE-HIV increased cell chemotaxis toward HIV secretome. The observation of SE-Drug and SE-HIV mediated alteration of monocyte transcriptome and cellular behavior reported herein is key to understanding the contribution of exosomes to long-term neuro, vascular, and mucosal perturbations associated with psychostimulants (methamphetamine, cocaine, opioids, and alcohol) comorbidity with HIV infection.
2019-09-20 | GSE129506 | GEO
Project description:Psychotropic drug-induced gene expression alterations in mouse striatum I
| PRJNA212394 | ENA