Comparative Effects of Arecoline, Caffeine, and Nicotine on Transcription Level in the NAc of Mice
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PROVIDER: PRJNA1177499 | ENA |
REPOSITORIES: ENA
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Project description:Though widely consumed, current research on the neural mechanisms of arecoline, caffeine, and nicotine remains limited, and the similarities and differences of these three substances on the nervous system are still not clear. This study used RNA-seq to analyze the gene expression in the nucleus accumbens (NAc) of mice, and further compared the behavioral changes through open field and conditioned place preference (CPP), exploring the effects of different psychoactive substances at the transcriptional and behavioral levels. Gene Ontology enrichment analysis revealed that nicotine and caffeine significantly alter biological processes related to synaptic function, and KEGG pathway analysis showed that the differentially expressed genes in the nicotine-treated group were significantly more enriched in pathways related to substance dependence compared to the other two treatment groups, with arecoline showing the least enrichment. Furthermore, only acute caffeine treatment significantly increased mouse activity, and only nicotine induced CPP. These results provided a scientific basis for evaluating the effects of arecoline, caffeine, and nicotine on the nervous system.
2024-11-11 | GSE280272 | GEO
Project description:Sex differences in behaviors relevant to nicotine addiction have been observed in rodent models and human subjects. Behavioral, imaging and epidemiological studies also suggest underlying sex differences in mesolimbic dopamine signaling pathways. In this study we evaluated the proteome in the ventral tegmental area (VTA) and nucleus accumbens (NAc) shell in male and female mice. Experimental groups included two mouse strains (C3H/HeJ and C57BL/6J) at baseline, a sub-chronic, rewarding regimen of nicotine in C3H/HeJ mice, and chronic nicotine administration and withdrawal in C57BL/6J mice. Isobaric labeling with a TMT 10-plex system, sample fractionation, and tandem mass spectrometry were used to quantify changes in protein abundance. Similar or greater numbers of differentially regulated proteins were found between sexes at baseline in C3H/HeJ or C57BL/6J mice than within sexes following their respective regimen of nicotine administration. Despite differences by sex, strain, and nicotine exposure parameters, glial fibrillary acidic protein (GFAP) and dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32, Ppp1r1b) were repeatedly identified as significantly altered proteins, especially in the VTA. Further, network analyses showed sex- and nicotine-dependent regulation of a number of signaling pathways, including dopaminergic signaling. Sub-chronic nicotine exposure in female mice increased proteins related to dopaminergic signaling in the NAc shell but decreased them in the VTA, whereas the opposite pattern was observed in male mice. In contrast, dopaminergic signaling pathways were similarly upregulated in both male and female VTA after chronic nicotine and withdrawal. Overall, this study identifies significant sex differences in the proteome of the mesolimbic system, at baseline and after nicotine reward or withdrawal, which may help explain differential trajectories and susceptibility to nicotine addiction in males and females.
2021-06-28 | PXD023859 | Pride
Project description:Purpose: This study aimed to identify differentially expressed genes including alternative splice variants in embryonic ventricles following in utero caffeine treatment. Methods: Pregnant CD-1 mice were injected with 20 mg/kg of caffeine or vehicle control daily from embryonic day (E) 6.5-9.5. On E10.5, total RNA was isolated from embryonic ventricles and used for transcriptomic RNA sequencing with Illumina HiSeq 2000 (1X75bp). RNA-seq reads were aligned to the mouse genome (build mm10) with the Tophat for Illumina tool in the PSU galaxy platform. Counting and annotation of RNA-seq reads as well as alternative splicing analysis were performed with Partek Genomics Suite version 6.11. Differential expression of gene and transcript reads between treatments was analyzed with R package EdgeR. Genes/transcripts with false discovery rate (FDR) less than 0.05 and absolute fold change greater than 1.5 were considered as significant. Differentially expressed genes were defined as genes with altered expression at either gene or transcript level. Unique differentially expressed genes were identified by combining the results from annotations with the RefSeq Transcripts (2013-05-10) or Ensembl Transcripts release 71 databases. Results: Differential expression analysis revealed that 59 genes and 451 transcripts were significantly up-regulated, and 65 genes and 398 transcripts were down-regulated by prenatal caffeine treatment (fold change >1.5 or <-1.5; p-value with FDR<0.05). In total, 900 unique genes were identified to have altered expression either at the gene or transcription level. Further analysis with Partek GS revealed that 183 genes had abnormal alternative splicing at the exon level after in utero caffeine treatment. Conclusions: In utero caffeine exposure caused gene expression changes in embryonic ventricles and these changes may lead to long-term effects on cardiac morphology and function. mRNA profiles in E10.5 heart ventricles treated with caffeine were generated by deep sequencing (n=2 for vehicle, n=3 for caffeine), using Illumina HiSeq 2000.
2015-01-07 | E-GEOD-56902 | biostudies-arrayexpress
Project description:Our previous research demonstrated that caffeine exposure on embryonic day (E) 8.5 increased body weight, altered cardiac morphology and function in adult male mice. However, these adverse effects were not observed in adenosine A1 receptor knockout (A1AR-/-) mice. Our hypothesis is that A1AR action mediates changes in DNA methylation patterns in mice exposed in utero to caffeine and that these changes in methylation lead to long-term effects in adult mice. To test this hypothesis, DNA Methylation 2.1M Deluxe Promoter Arrays (NimbleGen) were used to examine the methylation patterns of DNA isolated from adult left ventricles of the A1AR knockout line exposed to 20 mg/kg caffeine at E8.5 in utero. In A1AR+/+ mice, 4,896 hypermethylated and 2,823 hypomethylated regions were discovered in the left ventricles of the caffeine group compared to the normal saline group. In A1AR-/- mice, 1,024 hypermethylated and 1,757 hypomethylated regions were found in the caffeine group. The differentially methylated regions (DMRs) in the caffeine treated A1AR+/+ hearts mapped to 6,148 genes, 4,853 promoters, 4,111 primary transcripts, 816 CpG islands, and 98 miRNAs. Functional annotation clustering of genes revealed that many genes were involved in the development of hypertrophic cardiomyopathy and other heart diseases, which may explain our earlier findings of thickening of the left ventricular wall after in utero caffeine treatment. The methylation changes in several DMRs, mef2c, ins2, tnnt2, and myh6, were validated by bisulfite sequencing. In summary, in utero caffeine exposure caused DNA methylation changes in adult left ventricles and that these changes may be mediated by A1ARs. Pregnant mice were injected at embryonic day 8.5 with 0.9% NaCl (vehicle) or 20 mg/kg caffeine in vehicle i.p. Pups were born and raised until 8-10 weeks of age. Analysis was performed on the following groups vehicle A1AR+/+ (veh+/+), vehicle A1AR-/- (veh-/-), caffeine A1AR+/+ (caff+/+), and caffeine A1AR-/- (caff-/-). Genomic DNA from left ventricles of adult male mice was used. Two biological replicates were measured for each group.
2015-12-19 | E-GEOD-43030 | biostudies-arrayexpress
Project description:Caffeine is a well-known purine alkaloid commonly found in coffee. Several lines of previous and recent evidence have shown that habitual coffee drinking is associated with lower risks for chronic kidney disease (CKD) and nephrolithiasis. However, cellular and molecular mechanisms underlying its renoprotective effects remain largely unknown due to a lack of knowledge on cellular adaptive response to caffeine. This study investigated cellular adaptive response of renal tubular cells to caffeine at the protein level. Cellular proteome of MDCK cells treated with caffeine at a physiologic concentration (100 μM) for 24 h was analyzed comparing with that of untreated cells by label-free quantitative proteomics. From a total of 936 proteins identified, comparative analysis revealed significant changes in levels of 148 proteins induced by caffeine. These significantly altered proteins were involved mainly in proteasome, ribosome, tricarboxylic acid (TCA) (or Krebs) cycle, DNA replication, spliceosome, biosynthesis of amino acid, carbon metabolism, nucleocytoplasmic transport, cell cycle, cytoplasmic translation, translation initiation, and mRNA metabolic process. Functional validation by various assays confirmed that caffeine decreased cell population at G2/M, increased cell population at G0/G1, increased level of ubiquitinated proteins, increased intracellular ATP and enhanced mitochondrial membrane potential in MDCK cells. These data may help unravelling molecular mechanisms underlying the biological effects of caffeine on renal tubular cells at cellular and protein levels.
2023-12-11 | PXD045313 | Pride
Project description:The Nicotine Metabolic Ratio (NMR), the ratio of two stable metabolites of nicotine, cotinine and trans-3’hydroxycotinin, is a determinant of the number of cigarettes smoked per day (CPD), of smoking topography, responsiveness to treatment via transdermal nicotine for smoking cessation, and carcinogen activation and level. The predominant gene involved in nicotine metabolism is CYP2A6, a highly polymorphic locus located in a cluster of P450 cytochrome protein loci on chr19q13. A recent study comprehensively modeling CYP2A6 genetic variation at seven polymorphisms and a related Nicotine Metabolic Ratio, the cotinine: cotinine+nicotine ratio, explains 72% of NMRC/C+N variation. These results suggest that additional genes may be contributing to nicotine and cotinine metabolism directly or via interaction with CYP2A6 or other genes. To identify additional genes that may influence the NMR, we conducted a genome-wide gene expression analysis of lymphoblastoid cell line (LCL) gene expression in a sample of monozygotic twins discordant for the NMR.
2015-09-30 | GSE51284 | GEO
Project description:Genetic variants in gene regulatory sequences can modify gene expression and mediate the molecular response to environmental stimuli. In addition, genotype–environment interactions (GxE) contribute to complex traits such as cardiovascular disease. Caffeine is the most widely consumed stimulant and is known to produce a vascular response. To investigate GxE for caffeine, we treated vascular endothelial cells with caffeine and used a massively parallel reporter assay to measure allelic effects on gene regulation for over 43,000 genetic variants. We identified 665 variants with allelic effects on gene regulation and 6 variants that regulate the gene expression response to caffeine (GxE, false discovery rate [FDR] < 5%). When overlapping our GxE results with expression quantitative trait loci colocalized with coronary artery disease and hypertension, we dissected their regulatory mechanisms and showed a modulatory role for caffeine. Our results demonstrate that massively parallel reporter assay is a powerful approach to identify and molecularly characterize GxE in the specific context of caffeine consumption.
2024-02-26 | GSE221514 | GEO
Project description:Purpose: This study aimed to identify differentially expressed genes including alternative splice variants in embryonic ventricles following in utero caffeine treatment. Methods: Pregnant CD-1 mice were injected with 20 mg/kg of caffeine or vehicle control daily from embryonic day (E) 6.5-9.5. On E10.5, total RNA was isolated from embryonic ventricles and used for transcriptomic RNA sequencing with Illumina HiSeq 2000 (1X75bp). RNA-seq reads were aligned to the mouse genome (build mm10) with the Tophat for Illumina tool in the PSU galaxy platform. Counting and annotation of RNA-seq reads as well as alternative splicing analysis were performed with Partek Genomics Suite version 6.11. Differential expression of gene and transcript reads between treatments was analyzed with R package EdgeR. Genes/transcripts with false discovery rate (FDR) less than 0.05 and absolute fold change greater than 1.5 were considered as significant. Differentially expressed genes were defined as genes with altered expression at either gene or transcript level. Unique differentially expressed genes were identified by combining the results from annotations with the RefSeq Transcripts (2013-05-10) or Ensembl Transcripts release 71 databases. Results: Differential expression analysis revealed that 59 genes and 451 transcripts were significantly up-regulated, and 65 genes and 398 transcripts were down-regulated by prenatal caffeine treatment (fold change >1.5 or <-1.5; p-value with FDR<0.05). In total, 900 unique genes were identified to have altered expression either at the gene or transcription level. Further analysis with Partek GS revealed that 183 genes had abnormal alternative splicing at the exon level after in utero caffeine treatment. Conclusions: In utero caffeine exposure caused gene expression changes in embryonic ventricles and these changes may lead to long-term effects on cardiac morphology and function.
2015-01-07 | GSE56902 | GEO
Project description:To screen for xenobiotic-metabolizing-enzyme genes (XME) induced by caffeine exposure, a microarray experiment (performed with a Drosophila pangenomic array (Agilent 4 X 44K) was carried out between control and individuals exposed to caffeine (18mM ). Among 23401 genes consistantly found in the three biological replicates, 13108 showed a significant variation. 749 genes were over-expressed whereas 1518 were under-expressed. Interestingly, several genes belonging to all major classes of detoxification enzymes including XME were among the most highly induced such as CYP12d1, CYP6a8 and CYP6d5. Caffeine ingestion induced gene expression in Drosophila melanogaster male thorax and abdomen was mesured at 12h after exposure to doses of 0, 18mM of caffeine. Three independant experiments were performed at each dose using different drosophila for each experiment.
2014-07-04 | E-GEOD-59084 | biostudies-arrayexpress
Project description:Our laboratory previous research confirmed that nicotine in cigarette smoke causes apoptosis in germ cells in the testis and it will increase the formation of autophagosomes in the cytoplasm of testicular stromal cells. In addition, nicotine, the main toxic substance in cigarette smoke, also affects telomerase activity of spermatogenic cells, shortens telomere length, and causes structural damage of chromosomes. It is worth noting that after nicotine treatment, the expression of proteins involved in cytoskeleton regulation and energy metabolism in mouse testis was significantly up-regulated, and the sperm motility of mice was improved after nicotine treatment. To investigate the underlying mechanism, C57BL/6J mice were divided into control and nicotine treated groups. Next generation RNA sequencing and bio-informatics analysis were carried out to analysis the effects of nicotine on the RNA profile of mice spermatozoa. The results of RNA-Seq showed that the number of reads in the control group was 2089729, and the number of reads in the nicotine-treated group was 1739093, and a total of 8699 transcripts were obtained. Expression level of some pathways remarkably changed after nicotine treatment.This experimental study are helpful to understand the mechanism of the effect of nicotine on sperm and help us to provide a way to study the effection of patern nicotine exposure on offspring development.
2021-07-31 | GSE155145 | GEO