GeneSet Information

Tier III GS408910 • Adolescent (P43) DBA/2J transcripts significantly altered in PFC by ethanol using S-score analysis at FDR < 0.05

DESCRIPTION:

DBA/2J males and females (n = 24/sex) were orally dosed with 4 g/kg ethanol (25% w/v in water by gavage) or water intermittently (2 days on/2 days off) on PND 29, 30, 33, 34, 37, 38, 41, and 42. Tissue was collected for gene expression studies at PND 43 (n = 22) and PND 66 (n = 19). Behaviorally naïve tissue from the PFC was collected 24 h (at PND 43) and 3 weeks (at PND 66) after the last ethanol binge (dose). Total RNA was analyzed for gene-level expression differences using Mouse Transcriptome Arrays v1.0. We performed an analysis using the S-score probe-level algorithm which we have previously shown to have increased sensitivity for differential expression analysis (Zhang et al., 2002; Kennedy et al., 2006). For this analysis, data was collapsed over sex to increase the power to detect differences between ethanol treatment versus controls and to focus on lasting differences following binge ethanol. To assess genes that were persistently regulated long-term following adolescent binge ethanol, we intersected the S-score analysis gene list significantly altered by ethanol in adolescents with the list obtained from adults.

LABEL:

Adolescent D2 transcripts sig. altered in PFC using S-score analysis at FDR < 0.05 (EtOH vs control)

SCORE TYPE:

Binary

DATE ADDED:

2024-08-09

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

Jennifer T Wolstenholme, Tariq Mahmood, Guy M Harris, Shahroze Abbas, Michael F Miles 

TITLE:

Intermittent Ethanol during Adolescence Leads to Lasting Behavioral Changes in Adulthood and Alters Gene Expression and Histone Methylation in the PFC

JOURNAL:

Frontiers in Molecular Neuroscience Sep 2017, Vol 10, pp. 1-14

ABSTRACT:

Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC) transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol's actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood. PUBMED: 29018328
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Annotation Information

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Frontal Lobe (D005625)
Behavior (D001519)
Myelin Sheath (D009186)
Gene Expression (D015870)
Power (Psychology) (D011209)
Adolescent (D000293)
Therapeutics (D013812)
Prefrontal Cortex (D017397)
Sensitivity and Specificity (D012680)
Tissues (D014024)
Reflex, Righting (D057897)
Memory Disorders (D008569)
Algorithms (D000465)
Chromatin (D002843)
Histones (D006657)
Anxiety (D001007)
Alcoholism (D000437)
Ethanol (D000431)
Methylation (D008745)
frontal association cortex (MA:0000906)
frontal cortex (MA:0000905)
chromatin (GO:0000785)
demethylation (GO:0070988)
methylation (GO:0032259)
righting reflex (GO:0060013)
gene expression (GO:0010467)
Score or penalty (EDAM_data:1772)
Prediction, detection and recognition (EDAM_operation:2423)
Transcriptomics (EDAM_topic:0203)
Gene expression data processing (EDAM_operation:2495)
Differential expression analysis (EDAM_operation:3223)
dibenz[a,h]anthracene (CHEBI:35299)
(-)-(2R,3R)-2,3-dihydroxybutanamide (CHEBI:28598)
ribonucleic acid (CHEBI:33697)
perfluorinated compound (CHEBI:134091)
Behavioral abnormality (HP:0000708)
alcohol abuse (DOID:1574)
anxiety disorder (DOID:2030)
total RNA (EFO:0004964)
anxiety disorder (EFO:0006788)
treatment (EFO:0000727)
genomic data (EFO:0004600)
gram per kilogram (EFO:0002897)
frontal cortex (UBERON:0001870)
tetrapod frontal bone (UBERON:0000209)
prefrontal bone (UBERON:0010750)
adult organism (UBERON:0007023)
prefrontal cortex (UBERON:0000451)
frontal lobe (UBERON:0016525)

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