The influence of adolescent nicotine exposure on ethanol intake brain gene expression
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ABSTRACT:
PROVIDER: PRJNA474041 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR7244510.fastq.gz | Fastqsanger.gz | |||
| SRR7244520.fastq.gz | Fastqsanger.gz | |||
| SRR7244511.fastq.gz | Fastqsanger.gz | |||
| SRR7244521.fastq.gz | Fastqsanger.gz | |||
| SRR7244512.fastq.gz | Fastqsanger.gz |
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Project description:Background: Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. Aim: The aim was to to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of both substances on brain gene expression. Methods: RNA was extracted from a randomly selected subset of mice (16 total; 4 samples from each experimental group). Whole brains (including cerebellum) were dissected. Total RNA was extracted with an RNeasy® Midi Kit (QIAGEN, Valencia, CA). RNA quality was assessed using an Agilent 2100 BioAnalyzer™. An Illumina TruSeq® Stranded mRNA Library Prep Kit (Illumina, San Diego, CA) was used for cDNA library preparation following the manufacturers’ protocol. Libraries were sequenced using an Illumina HiSeq 2500 (Illumina, San Diego, CA). Trimmomatic was used to remove sequencing adapters and low-quality ends. The cleaned dataset was analyzed with the Tuxedo pipeline. Subsequently, readings were mapped to the mouse reference genome (Ensembl GRCm38, mm10) using TopHat2 software (http://tophat.cbcb.umd.edu/). The ‘--library_type’ parameter was set to ‘fr-firststrand’. Default settings were preserved for all other TopHat2 parameters. The resulting alignments files from TopHat2 were used to generate a transcriptome assembly. Gene expression was calculated for each condition using the Cufflinks and Cuffmerge utilities. Cuffdiff2 with default settings was used to identify transcripts that were differentially expressed between each treatment group compared to the water only control group.The significance threshold was set at q < 0.05 (FDR corrected). Finally, a Fisher’s exact test was performed using the GeneOverlap R package to test the significance of DEG overlaps. Gene co-expression networks were identified using the Weighted Gene Co-expression Network Analysis (WGCNA) package. Results: RNA Integrity Number (RIN) was on average 8.23 ± 0.26 for all samples, suggesting high RNA integrity and quality. On average, 43 million, 150 base pair single end reads were generated for each sample and used in the analysis. The resulting alignments files from TopHat2 had an average mapping rate of 87.4%.
2018-06-02 | GSE115188 | GEO
Project description:We used microarrays to determine the effect of prenatal nicotine exposure on gene expression profiles in the striatum of adolescent rats. We found a number of immediate early genes to be differentially expressed due to food-restriction. We compared control (n=8), nicotine exposed (n=7) and a group of animals matched to the food intake of nicotine exposed animals (n=10) to identify gene expression changes associated with prenatal nicotine exposure
2013-09-06 | E-GEOD-50607 | biostudies-arrayexpress
Project description:Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA- and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanol-induced changes at the transcription level with differential exon-use and cryptic transcription analysis – a hallmark of decreased H3K36me3. Here, we found ethanol-induced changes to the gene expression and H3K36me3-regulation of synaptic-related genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function.
2023-02-21 | GSE220745 | GEO
Project description:Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA- and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanol-induced changes at the transcription level with differential exon-use and cryptic transcription analysis – a hallmark of decreased H3K36me3. Here, we found ethanol-induced changes to the gene expression and H3K36me3-regulation of synaptic-related genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function.
2023-02-21 | GSE220742 | GEO
Project description:Medial habenular (mHb) cholinergic neurons that project to the interpeduncular nucleus (IPn) regulate aversive behavioral responses to nicotine that protect against tobacco addiction. Little is known about the nicotine-evoked cellular or molecular adaptations in these neurons that influence the development of the smoking habit. Using in vivo calcium imaging and single-cell RNA sequencing, we show that a dose of nicotine that stimulates mHb neural activity evokes robust transcriptional plasticity in neuronal and non-neuronal cells in the mHb, including upregulated expression of Hedgehog-interacting protein (HHIP) in putative cholinergic neurons. Allelic variation in HHIP confers risk for smoking-related diseases including chronic obstructive pulmonary disease and lung cancer, but underlying mechanisms of action are unclear. Using Translating Ribosome Affinity Purification (TRAP) sequencing and RNAscope, we confirmed that Hhip transcripts are highly enriched in mHb cholinergic neurons. HHIP mutant mice exhibit hundreds of differentially expressed transcripts in the mHb and perturbed transcriptional responses to nicotine. Moreover, acute in vivo CRISPR/Cas9-mediated genomic cleavage of mHb Hhip attenuated noxious responses to nicotine and increased intravenous nicotine self-administration behavior in mice. In vitro knockdown of Hhip reduces intracellular calcium release to nicotine and increases Gli activity. These findings suggest that HHIP acts in the mHb to regulate nicotine intake and that HHIP alleles may increase vulnerability to smoking-related diseases by modulating mHb signaling and enhancing the addictive properties of tobacco.
2022-11-06 | GSE217000 | GEO
Project description:We used microarrays to determine the effect of prenatal nicotine exposure on gene expression profiles in the striatum of adolescent rats. We found a number of immediate early genes to be differentially expressed due to food-restriction.
2013-09-06 | GSE50607 | GEO
Project description:Effect of ethanol or nicotine exposure on gene expression compared to control. Duplicate arrays from ethanol or nicotine treated animals compared with triplicate arrays from paired control animals. In total 4 treatment arrays (2 ethanol, 2 nicotine) and 3 control arrays (from control animals treated in parallel with ethanol-treated fish and nicotine-treated fish.)
2008-05-01 | E-MEXP-1301 | biostudies-arrayexpress
Project description:Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of these substances on brain gene expression. Forty-three adolescent female C57BL/6J mice were assigned to four groups. In the first phase of the experiment, adolescent mice (PND 36-41 days) were exposed to three bottles filled with water or nicotine (200 ?g/ml) for 22 h a day and a single bottle of water 2 h a day for six days. In the second phase (PND 42-45 days), the 4-day Drinking-in-the-Dark paradigm consisting of access to 20% v/v ethanol or water for 2h or 4h (the last day) was overlaid during the time when the mice did not have nicotine available. Ethanol consumption (g/kg) and blood ethanol concentrations (BEC, mg %) were measured on the final day and whole brains including the cerebellum, were dissected for RNA sequencing. Differentially expressed genes (DEG) were detected with CuffDiff and gene networks were built using WGCNA. Prior nicotine exposure increased ethanol consumption and resulting BEC. Significant DEG and biological pathways found in the group exposed to both nicotine and ethanol included genes important in stress-related neuropeptide signaling, hypothalamic-pituitary-adrenal (HPA) axis activity, glutamate release, GABA signaling, and dopamine release. These results replicate our earlier findings that nicotine exposure during adolescence increases ethanol consumption and extends this work by examining gene expression differences which could mediate these behavioral effects.
| S-EPMC6005571 | biostudies-literature
Project description:The in utero environment is a critical determinant of the immediate and future health of the developing fetus. Two of the most commonly used drugs during pregnancy are alcohol and nicotine. While prolonged gestational exposure to alcohol or nicotine has been associated with a range of adverse outcomes in the offspring, the consequences of exposure during early gestation only are less well understood. Here, we use mouse models of relatively moderate early gestational ethanol or nicotine exposure to profile gene expression in whole male embryos at 9.5 days post coitum using an Illumina microarray.
2021-08-18 | GSE94347 | GEO
Project description:The habenula, an ancient small brain area in the epithalamus, densely expresses nicotinic acetylcholine receptors and is critical for nicotine intake and aversion. As such, identification of strategies to manipulate habenular activity may yield new approaches to treat nicotine addiction. Here we show that GPR151, an orphan G protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents is expressed at presynaptic membranes and synaptic vesicles, and associates with synaptic components controlling vesicle release and ion transport. Deletion of Gpr151 inhibits evoked neurotransmission but enhances spontaneous miniature synaptic currents and eliminates short-term plasticity induced by nicotine. We find that GPR151 couples to the G-alpha inhibitory protein Gao1 to reduce cAMP levels in mice and in GPR151 expressing cell lines that are amenable to ligand screens. Gpr151-KO mice show diminished behavioral responses to nicotine, and self-administer greater quantities of the drug, phenotypes rescued by viral re-expression of Gpr151 in the habenula. These data identify GPR151 as a critical modulator of habenular function that controls nicotine addiction vulnerability.
2020-01-18 | GSE143854 | GEO