RNA Sequencing of the Long-Evans Rat Anterior Cingulate Cortex and Nucleus Accumbens Reveals Sex-Specific Developmental Changes and a Lingering Impact of Prenatal and Adolescent Alcohol Exposure in Females Only II
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE327221 | GEO | 2026/06/03
REPOSITORIES: GEO
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Project description:Prenatal alcohol exposure through maternal drinking and adolescent alcohol intake are the two most common forms of early alcohol consumption, which may produce synergistic impacts on health. Yet, few preclinical studies have used double-hit models to examine how effects manifest across sex and lifespan. In this study, RNA-seq was used to analyze the effects of ethanol on the anterior cingulate cortex (ACC) of adult and adolescent male and female Long-Evans rats (n = 5+ per group, N = 144) that were exposed to ethanol during gestation, adolescence, or both. During prenatal exposure, dams received either ethanol liquid diet (PAE group: 2.2% v/v EtOH on gestational day [G]6-8, 4.5% on G9-10, and 6.7% on G11-20) or control diets (PF pair-fed, FCL free-choice liquid diet). In adolescence, offspring were exposed to alcohol (AAE: 11h of 10% EtOH in tap water, 1h water access, 12h of water deprivation daily from prenatal [P] day 27-41) or given ad libitum water access (VEH). Brains were collected on P42 (adolescence) and P90 (adulthood). Differentially expressed genes (DEGs) were identified via DESeq2, with the resulting p values adjusted using the Benjamini-Hochberg correction (≤ 0.05). Surprisingly, there were minimal effects of any ethanol on males in adolescence, and none enduring in adulthood. In contrast, adult females with a double-hit history showed the most robust change: 4 genes were found to be downregulated (C3, Syt6, Spetex2l2, and Akap12) and 19 upregulated. These genes did not align to a specific pathway, yet more than one (i.e. C3, Akap12) were associated with immune function (e.g. complement system, glial function). It is interesting to note that these changes represent enduring alterations to baseline ACC state 48 days after the last ethanol exposure without a subsequent challenge. When examining ethanol-naïve controls, we found that between P42 and P90, both sexes were undergoing significant change. 451 DEGs were identified for males and 95 for females, yet only 36 DEGs overlapped between the sexes, demonstrating that even in the period of late adolescence (P42 onward), males and females were on different trajectories of development. Together, these findings form a foundation for examining sex-specific ACC development and female-specific vulnerability to damage from the double-hit ethanol model.
2026-06-03 | GSE327217 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 to 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in the central nucleus of the amygdala (CeA) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.
2013-07-20 | E-GEOD-49040 | biostudies-arrayexpress
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in brain nucleus accumbens shell (Acb-sh) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.
2013-07-20 | E-GEOD-49041 | biostudies-arrayexpress
Project description:Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens
2023-09-18 | GSE242910 | GEO
Project description:Mephedrone (Meph) is a novel psychostimulant whose recreational consumption is often associated to other drugs, especially alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern. We studied, in adolescent CD-1 mice, whether low-moderate doses of EtOH could enhance the psychostimulant (locomotor acivity) and reinforcing (conditioned place preference, CPP) effects of mephedrone. Simultaneously we also determined the most relevant transcriptional changes associated to a reinforcing treatment. A single dose of Meph (10 mg/kg, sc) induced an increase of about 100% in locomotor activity, which was a further enhanced by 40% when associated with a dose of EtOH (1 g/kg). The hyperlocomotion was partially antagonized by ketanserin and haloperidol, but only haloperidol blocked the potentiation induced by EtOH. Furthermore, Meph (25 mg/kg) induced significant positive conditioning, which increased by 70% when administered with 0.75 mg/kg EtOH. Microarray analysis of mRNA extracted from anterior striata of the mice used in CPP experiments reported significant modifications in genes related with neurotransmission and synaptic plasticity, which were further validated by Real-time PCR for all three drug-treated groups. Four groups were compared in the study: adolescent Swiss CD-1 mice treated with saline, ethanol, mephedrone or mephedrone + ethanol during the conditioned place preference (CPP) ten-day procedure, aimed at evaluating reward. Twelve samples are provided, which correspond to triplicates of each treatment group. The samples provided were subsequently normalized and analyzed using the GeneSpring GX 7.3.1 software.
2016-08-01 | E-GEOD-58279 | biostudies-arrayexpress
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function.
2013-07-20 | GSE49041 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function.
2013-07-20 | GSE49040 | GEO
Project description:The objective of this study was to determine changes in gene expression in the ventral tegmental area (VTA) following loss-of-control alcohol drinking by alcohol-preferring (P) rats. Adult female P rats (n = 7) were given concurrent access to 10, 20 and 30% EtOH for four 1-hr sessions daily for 10 weeks followed by 2 cycles of 2 weeks of abstinence and 2 weeks of EtOH access. Rats were killed by decapitation 3 hr after the 4th daily EtOH-access session at the end of the second 2-week relapse period. An age-matched water control group of female P rats (n = 8) was also killed. RNA was prepared from micropunch samples of the VTA from individual rats; analyses were conducted with Affymetrix Rat 230.2 chips. Ethanol intakes were 1.5-2.5 g/kg per sessions, resulting in blood levels >200 mg% at the end of the 4th session. There were 211 named genes that were significantly different (FDR = 0.1) between the water and EtOH groups. Bioinformatics analyses indicated alterations in (a) transcription factors that reduced excitation-coupled transcription and promoted exocitotic neuronal damage involving clusters of genes associated with Nfkbia, Fos and Srebf1; (b) genes that reduced cholesterol and fatty acid synthesis, and increased protein degradation; and (c) genes involved in cell-to-cell interactions and regulation of the actin cytoskeleton. Among the named genes, there were 62 genes in common with differences between alcohol-naïve P and non-preferring (NP) rats, with 43 of the genes changing in the opposite direction following excessive binge-like drinking. These genes are involved in a pro-inflammatory response, and enhanced response to glucocorticoids and steroid hormones. Overall, the results of this study indicated that excessive binge-like alcohol drinking by P rats may be altering the expression of genes that promote neuronal damage.
2013-06-01 | GSE42578 | GEO
Project description:Moderate alcohol consumption during pregnancy can result in a heterogeneous range of neurobehavioural and cognitive effects, termed fetal alcohol spectrum disorders (FASD). We have developed a mouse moder of FASD that involves moderate ethanol exposure throughout gestation achieved by voluntary maternal consumption. This model results in phenotypes relevant to FASD. Since ethanol is known to directly affect the expression of genes in the developing brain leading to abnormal cell death, changes to cell proliferation, migration, and differentiation, and potential changes to epigenetic patterning, we hypothesize that this leaves a long-term footprint on the adult brain. However, the long-term effects of prenatal ethanol exposure on brain gene expression, when behavioural phenotypes are apparent, are unclear. We used two independent microarray experiments and focused on the genes identified by both to evaluate the genome-wide alterations to the adult brain transcriptome caused by prenatal ethanol exposure via moderate maternal drinking. To generate samples, two independent groups of female C57BL/6J mice were given access to 10% ethanol in water or water only. Control females had access to water only. Females were mated and continued to drink from gestational day 0 to pup postnatal day 10. Whole brain RNA from adult (postnatal day 70) male ethanol-exposed offspring was extracted. For experiment 1, RNA samples from three mice were pooled to reduce litter effects and the pooled samples were hybridized on Affymetrix arrays (2 control and 2 ethanol chips, total n=12 mice). For experiment 2, RNA from two mice were pooled per chip and three arrays per treatment were used (3 control, 3 ethanol, total n=12 mice).
2011-12-10 | E-GEOD-34305 | biostudies-arrayexpress
Project description:Tobacco use and alcohol consumption are two major contributing factors for head and neck squamous cell carcinoma (HNSCC) carcinogenesis. We combined the 4-nitroquinoline-1-oxide (4-NQO) oral carcinogenesis mouse model and the Meadows-Cook alcohol mouse models and performed next generation genome-wide RNA-sequencing of tongues. We determined changes in transcript levels in four groups: 4-NQO followed by ethanol treatment (4-NQO/EtOH), 4-NQO followed by normal drinking water (4-NQO/Untr.), vehicle control followed by ethanol treatment (V.C./EtOH), and vehicle control followed by normal drinking water (V.C./Untr.). We found that the 494 gene transcripts were significantly changed (at least a 2-fold change where p<0.05) in the V.C./EtOH group compared to the V.C./Untr. group. The 4-NQO/Untr. group had 1,808 transcripts significantly changed compared to the V.C./Untr group, while the 4-NQO/EtOH group had 3,606 significantly changed transcripts as compared to the V.C/Untr. group. This study is the first to show that 4-NQO followed by ethanol cause the largest number of changes in transcript levels in the tongue.
2015-10-06 | GSE62125 | GEO