CD4+ Tcell : control vs cocaine treated
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE46398 | GEO | 2013/05/28
SECONDARY ACCESSION(S): PRJNA200337
REPOSITORIES: GEO
Similar Datasets
Project description:Changes in miRNA profile of CD4+ T cells treated with cocaine 6 samples were analysed, 3 control and 3 treated with cocaine
2013-05-28 | E-GEOD-46398 | biostudies-arrayexpress
Project description:We cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically-enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes.
2011-05-13 | GSE29261 | GEO
Project description:We cataloged miRNA expression in the nucleus accumbens and at striatal synapses in control and chronically cocaine-treated mice. We identified cocaine-responsive miRNAs, synaptically-enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several predicted synaptic target genes. Analysis of small RNA from Mus musculus nucleus accumbens (NAc) and postsynaptic densities (PSD) with and without chronic cocaine treatment.
2011-05-13 | E-GEOD-29261 | biostudies-arrayexpress
Project description:BMVEC cells treated with cocaine and matched controls were analyzed with diaPASEF on a TIMSTOF Flex instrument.
2023-07-26 | MSV000092529 | MassIVE
Project description:Repeated exposure to cocaine causes sensitized behavioral responses and increased dendritic spines on medium spiny neurons of the nucleus accumbens (NAc). We find that cocaine regulates myocyte enhancer factor 2 (MEF2) transcription factors to control these two processes in vivo. Cocaine suppresses striatal MEF2 activity in part through a novel mechanism involving cAMP, the regulator of calmodulin signaling (RCS), and calcineurin. We show that reducing MEF2 activity in the NAc in vivo is required for the cocaine-induced increases in dendritic spine density. Surprisingly, we find that increasing MEF2 activity in the NAc, which blocks the cocaine-induced increase in dendritic spine density, enhances sensitized behavioral responses to cocaine. Together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine, and suggest that reducing MEF2 activity (and increasing spine density) in NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine.
2008-08-24 | GSE11939 | GEO
Project description:The 10 samples below represent a study where gene expression levels were measured in 5 different parts of the rat brain under cocaine-treated (GSM4696, GSM4698 - GSM4701) and saline-treated control (GSM4702 - GSM4706) conditions. The regions studied were amygdala (amy), caudate putamen (cpu), nucleus acumbens (na), prefrontal cortex (cpu), and the ventral tegmental area (vta). The data were analyzed using two different computational techniques, viz. singular value decomposition (SVD) and self-organizing maps (SOM), to identify a common set of genes that were regulated by cocaine administration.
2007-10-10 | E-GEOD-340 | biostudies-arrayexpress
Project description:Repeated exposure to cocaine causes sensitized behavioral responses and increased dendritic spines on medium spiny neurons of the nucleus accumbens (NAc). We find that cocaine regulates myocyte enhancer factor 2 (MEF2) transcription factors to control these two processes in vivo. Cocaine suppresses striatal MEF2 activity in part through a novel mechanism involving cAMP, the regulator of calmodulin signaling (RCS), and calcineurin. We show that reducing MEF2 activity in the NAc in vivo is required for the cocaine-induced increases in dendritic spine density. Surprisingly, we find that increasing MEF2 activity in the NAc, which blocks the cocaine-induced increase in dendritic spine density, enhances sensitized behavioral responses to cocaine. Together, our findings implicate MEF2 as a key regulator of structural synapse plasticity and sensitized responses to cocaine, and suggest that reducing MEF2 activity (and increasing spine density) in NAc may be a compensatory mechanism to limit long-lasting maladaptive behavioral responses to cocaine. Mice were treated for 7 days with daily injections of cocaine (20 mg/kg) and sacrificed 24 hrs later. Chromatin from bilateral punches of NAc was immunoprecipitated with an antibody against MEF2A as described previously with minor modifications (Renthal et al., 2007). Chromatin was sonicated to an average of ~500 bp and immunoprepitated with antibody against MEF2A (Santa Cruz, sc-313) or an IgG control (Upstate/Millipore). Antibody-bound chromatin was precipitated using Protein A beads from Upstate (06-157), which were washed with low salt, high salt, and LiCl buffers to remove non-specific DNA binding. Eluted chromatin was reverse-crosslinked at 65oC in the presence of proteinase K and EDTA. DNA was purified by chloroform extraction/ethanol precipitation and the enrichment of specific promoters was amplified by ligation-mediated PCR for genome-wide analysis (Sikder et al., 2006). Amplified DNA was then labeled with Cy3 (input-enriched) or Cy5 (MEF2-enriched) and hybridized to Nimblegen (Madison, WI) MM8 mouse promoter arrays. Bilateral nucleus accumbens from eight mice were pooled for microarray analysis.
2008-08-24 | E-GEOD-11939 | biostudies-arrayexpress
Project description:Cocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-accumbal pathway during acute withdrawal and protracted abstinence following escalated cocaine intake. Small RNA sequencing (sRNA-seq) was used to profile miRNA transcriptomic changes in the cortico-accumbal pathway [infralimbic- and prelimbic-prefrontal cortex (IL and PL) and nucleus accumbens (NAc)] of rats with extended access to cocaine self-administration followed by an 18-h withdrawal or a 4-week abstinence. An 18-h withdrawal led to differential expression (fold-change > 1.5 and p < 0.05) of 21 miRNAs in the IL, 18 miRNAs in the PL, and two miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in the following pathways: gap junctions, neurotrophin signaling, MAPK signaling, and cocaine addiction. Moreover, a 4-week abstinence led to differential expression (fold-change > 1.5 and p < 0.05) of 23 miRNAs in the IL, seven in the PL, and five miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in pathways including gap junctions, cocaine addiction, MAPK signaling, glutamatergic synapse, morphine addiction, and amphetamine addiction. Additionally, the expression levels of several miRNAs differentially expressed in either the IL or the NAc were significantly correlated with addiction behaviors. Our findings highlight the impact of acute and protracted abstinence from escalated cocaine intake on miRNA expression in the cortico-accumbal pathway, a key circuit in addiction, and suggest developing novel biomarkers and therapeutic approaches to prevent relapse by targeting abstinence-associated miRNAs and their regulated mRNAs.
2023-08-30 | GSE212651 | GEO
Project description:Several recent reports show that the cerebral cortex in humans and animals with altered expressions of Wnt/cadherin network-associate molecules display cytoarchitectural abnormalities reminiscent of cortical dysplasias seen in some (mouse-, rat-, and monkey-based) animal models of prenatal cocaine exposure. Therefore, we employed oligo microarrays followed by real-time RT-PCR to compare expressions of genes involved in Wnt and cadherin systems in the cerebral wall of 18-day-old (E18) fetuses from cocaine-treated (20 mg/kg cocaine, s.c., b.i.d., E8-18) and drug-naive (saline, s.c.) mice. The pregnant mice chronically treated with cocaine in the above-described manner represent one of the animal models producing offspring with widespread cortical dysplasias. Out of more than 150 relevant genes in the arrays, 32 were upregulated and 9 were downregulated in cocaine-exposed fetuses. The majority of these genes (30 out of 41) were similarly affected in the frontal and occipital regions of the cerebral wall. We also used Western immunoblotting to examine the ability of cocaine to regulate the protein levels of beta-catenin, the key functional component of both Wnt and cadherin systems. While the total cell levels of beta-catenin were increased throughout the cerebral wall of cocaine-exposed fetuses, its nuclear (gene-transcription driving) levels remained unaltered. This suggests a transcription-unrelated role for cocaine-induced upregulation of this protein. Overall, our findings point to an intriguing possibility that that cerebral cortical dysplasias observed in several animal models of prenatal cocaine exposure may be at least in part related to alterations in the Wnt/cadherin molecular network. It has been demonstrated that exposure to cocaine increases cell death in the fetal CNS. To examine the molecular mechanisms of this effect, we employed mouse oligo microarrays followed by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) to compare expressions of apoptosis-related genes in the cerebral wall of 18-day-old (E18) fetuses from cocaine-treated (20 mg/kg cocaine, s.c., b.i.d., E8th-E18th) and drug-naive (saline, s.c.) mice. Out of approximately 400 relevant genes in the arrays, 53 showed alterations in expression in cocaine-exposed fetuses. Upregulation was observed in 35 proapoptotic and 8 antiapoptotic genes; 4 proapoptotic and 6 antiapoptotic genes were down-regulated. The affected genes encode a wide range of apoptosis-related proteins, including death receptors (NTF-R1, NTF-R2, DR3, DR5, LTbeta-R, GITR, P57 TR-1) and their adaptor and regulatory proteins (MASGE-D1, TRAF-2, SIVA, MET, FLIP, FAIM, IAP1, ATFA), members of transcription regulatory pathways (JNK, NF-kappaB, P53), members of BCL-2 family of proteins (BID, BAD, BAX, BIK, NIP21, NIP3, NIX, BCL-2), DNA damage sensor (PARP-1), caspases and their substrates and regulatory proteins (caspases 8, 4, 9, and 3, ACINUS, CIDE-A, CIDE-B, GAS2), mitochondrially released factors (cytochrome c, AIF, PRG3), specific endoplasmic reticulum- and oxidative stress-associated factors (BACH2, ABL1, ALG2, CHOP), members of cell survival AKT and HSP70 pathways (PIK3GA, PTEN, HSP70, BAG1, BAG2), and others. This suggests that cocaine affects survival of developing cerebral cells via multiple apoptosis-regulating mechanisms. Experiment Overall Design: Animals Experiment Overall Design: Timed pregnant Swiss Webster (CFW; Charles River Experiment Overall Design: Lab. Wilmington, MA) dams were maintained in individual Experiment Overall Design: cages in a climate-controlled room on a 12/12-h light/ Experiment Overall Design: dark cycle. They were divided into two groups. The first Experiment Overall Design: (experimental) group received subcutaneous (at the dorsum Experiment Overall Design: of the neck) injections of 20 mg/kg cocaine hydrochloride Experiment Overall Design: (Research Technology Branch, National Institute Experiment Overall Design: of Drug Abuse, Rockville, MD) dissolved in 200 mkl of Experiment Overall Design: 0.9% saline, twice a day (at 8:00 AM and 8:00 PM) from Experiment Overall Design: 8th through 18th day of pregnancy (E8âE18). The second Experiment Overall Design: (control) group was subjected to the same schedule of Experiment Overall Design: 0.9% saline only injections. The cocaine treatment was Experiment Overall Design: designed to replicate the one capable of reducing cerebral Experiment Overall Design: cortical mass in mouse offspring. Also, the Experiment Overall Design: relatively protracted period the chronic treatment was Experiment Overall Design: chosen to maximize the changes in the tissue expression Experiment Overall Design: of cocaine-regulated genes of interest. Throughout the Experiment Overall Design: treatment, all mice were weighed daily, and, from E8, the Experiment Overall Design: control and experimental animals were pair-fed, with the Experiment Overall Design: daily amount of food (Mouse Chow; Ralston Purina Saint Experiment Overall Design: Louis, MO) provided to each control dam being matched Experiment Overall Design: to that consumed by the paired experimental dam. Water Experiment Overall Design: was available ad libitum. We found that this feeding Experiment Overall Design: regiment resulted in similar weight gains from E8 to E18 Experiment Overall Design: in both experimental and control animal groups Experiment Overall Design: (46.41F0.45% and 44.99F0.59% respectively). On E18, Experiment Overall Design: 1 h after the morning treatment, the animals were Experiment Overall Design: anesthetized by peritoneal injection of 50 mg/kg sodium Experiment Overall Design: pentobarbital (Abbott Lab., Abbott Park, IL) and their Experiment Overall Design: uteri were removed. The frontal cerebral wall (containing Experiment Overall Design: cerebral cortex and underlying transient cortical zones Experiment Overall Design: anterior to the striatal level) and the occipital cerebral wall Experiment Overall Design: (containing cerebral cortex and underlying transient Experiment Overall Design: cortical zones posterior to the level of the hippocampus) Experiment Overall Design: were dissected from the fetuses and stored in liquid Experiment Overall Design: nitrogen prior to analysis. The animal experimentations Experiment Overall Design: used in this study were approved by the University of Experiment Overall Design: Maryland Animal Care and Use Committee. Experiment Overall Design: Microarray Experiment Overall Design: Tissue from two control and two experimental fetuses Experiment Overall Design: were used in the processing of a single microarray slide Experiment Overall Design: (Part G4121A, Agilent Technol). Five slides were processed Experiment Overall Design: per region of the fetal cerebral wall. For a given region, the Experiment Overall Design: tissue for each microarray slide was obtained from a Experiment Overall Design: separate set of control and experimental litters. Total RNA Experiment Overall Design: was isolated using TRIzol Reagent (Invitrogen, Carlsbad, Experiment Overall Design: CA). The yield of total RNA was determined by absorbance Experiment Overall Design: at 260 nm on a DU 640 Spectrophotometer (Beckman Experiment Overall Design: Coulter, Fullerton, CA). The 260/280 nm ratios of the Experiment Overall Design: samples were >1.8. For each assay, 5 mkg of RNA from Experiment Overall Design: control tissue and 5 mkg of RNA from experimental tissue Experiment Overall Design: were reverse transcribed using 3DNA Array Detection Kit Experiment Overall Design: (Genesphere, Hatfield, PA) with primers containing different Experiment Overall Design: dcaptureT sequences for control and experimental Experiment Overall Design: samples. SuperScript II Reverse Transcriptase for these Experiment Overall Design: reactions was purchased from Gibco BRL (Gaithersburg, Experiment Overall Design: MD). The resultant cDNAs were hybridized to microarray Experiment Overall Design: slides for 16 h in Agilent Hybridization Buffer (Agilent Experiment Overall Design: Technol) at 60 8C. Upon completion of the hybridization, Experiment Overall Design: the slides were washed for 10 min with 0.005% Triton in Experiment Overall Design: 6xsodium chloride/sodium citrate buffer (pH 7; SSC) at Experiment Overall Design: room temperature and then for five more min with 0.005% Experiment Overall Design: Triton in 0.1xSSC and 1 more minute in 0.1xSSC (pH 7), Experiment Overall Design: both at 4 8C. Washed slides were air-dried for 30 s. For Experiment Overall Design: fluorescent labeling of microarray-bound cDNA, the slides Experiment Overall Design: were incubated for 3 h at 65 8C with Capture Reagent Experiment Overall Design: Hybridization Mixture from 3DNA Array Detection Kit Experiment Overall Design: (Genesphere). In this mixture, Alexa 546 fluorochromeincorporating Experiment Overall Design: dendrimers contained single-stranded arms Experiment Overall Design: complimentary to the dcaptureT sequences used in the Experiment Overall Design: reverse transcription of RNA from control tissue, while Experiment Overall Design: Alexa 647 fluorochrome-incorporating dendrimers contained Experiment Overall Design: arms complimentary to the capture sequences used Experiment Overall Design: in reverse transcription of RNA from experimental tissue. Experiment Overall Design: The labeling reaction was terminated by washing of the Experiment Overall Design: microarray slides at room temperature for 10 min with Experiment Overall Design: 0.005% Triton in 2xSSC and for another 10 min with in Experiment Overall Design: 0.2xSSC. After that, the slides were air-dried for 30 s. The Experiment Overall Design: processed microarray slides were scanned at 10 Am Experiment Overall Design: resolution on a GenePix 4100A scanner (Axon Instr., Union Experiment Overall Design: City, CA) with the laser excitation at 532 nm [emission filter Experiment Overall Design: 575DF35 (green); photomultiplier voltage 550] for Alexa Experiment Overall Design: 546 (control samples) and the laser excitation at 635 nm Experiment Overall Design: [emission filter 670DF40 (red); photomultiplier voltage Experiment Overall Design: 695] for Alexa 647 (experimental samples). The signals Experiment Overall Design: were converted into 16-bits-per pixel resolution images, Experiment Overall Design: providing color depth of 65,536 levels. The densitometry Experiment Overall Design: was performed with GenePix Pro 4.1 software (Axon Instr.). Experiment Overall Design: Background was subtracted using the dlocal background Experiment Overall Design: correctionT procedure available in the software. Quality control utilized 255 positive controls, 161 negative controls Experiment Overall Design: and 646 QC-spots present on Agilentâs arrays. For Experiment Overall Design: replicates within a slide, median signal values were Experiment Overall Design: calculated. For each array, the data were normalized in Experiment Overall Design: Acuity 3.1 software (Axon Instr.) by applying locally Experiment Overall Design: weighted scatterplot smoothing (LOWESS) transformation. Experiment Overall Design: The between array scale normalization Experiment Overall Design: was done using intensity log10 ratio distribution box plots (GeneSight Experiment Overall Design: software, BioDiscovery, El Segundo, CA) for verification. Experiment Overall Design: Statistical analysis of the normalized data was conducted Experiment Overall Design: by the Significant Analyses for Microarray Algorithm Experiment Overall Design: (SAM) using Excel macros available at the Stanford SAM website. Experiment Overall Design: In the analyses of both frontal and occipital regions of the fetal cerebral wall, Experiment Overall Design: the cut-off thresholds were set to identify the maximum Experiment Overall Design: number of cocaine exposure-regulated genes at the minimal Experiment Overall Design: false discovery rate (FDR) allowed by SAM for a given set Experiment Overall Design: of microarray data. For both regions, the FDR rates were Experiment Overall Design: <0.5%. The apoptosis and Wnt pathway-related genes were identified with Pathway Assist 2.0 software (Stratagene, La Jolla, CA). Experiment Overall Design: This was followed by manual review of literature for each Experiment Overall Design: identified gene.
2008-06-15 | E-GEOD-6628 | biostudies-arrayexpress
Project description:We aimed to identify how loss of the cap methyltransferase RNMT affected the ribosomes and ribosome-associated proteins in activated CD4 T cells.
2021-05-13 | PXD023832 | Pride