GeneSet Information

Tier IV GS408903 • Differentially expressed genes in prefrontal cortex significantly altered in adolescent (P43) DBA/2J mice 24 hrs post treatment (EtOH vs control)_pvalue

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. Two complementary analyses were conducted to interrogate differential gene expression at each age. Gene Ontology over-representation analysis identified six categories involved in oligodendrocyte development and myelination as the primary Biological Processes altered by adolescent binge ethanol. For transcript IDs significant for the interaction between sex and adolescent treatment, Gene Ontology analysis only identified two over-represented cellular components: ER chaperone component and smooth ER. When comparing gene expression between adolescent males vs. females, most of the differentially expressed genes either resided on the Y chromosome (Ddx3y, Eif2s3y, Kdm5d, Uty), or are known to escape X-inactivation (Ddx3x, Eif2s3x, Kdm5c, Kdm6a) in mice (Yang et al., 2010). Over-represented Gene Ontology categories (Supplementary Table 2) reflect their processes, such as histone demethylase activity, angiotensin catabolic processes in blood, cell adhesion and regulation of gap junction assembly. Genes in this geneset are all significantly altered as a main effect of treatment, sex, or the interaction between treatment and sex (p < 0.01).

LABEL:

DEG PFC in adolescent D2 mice 24hr post treatment_pvalue

SCORE TYPE:

P-Value

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

No sequence read archive data associated with this GeneSet.


Frontal Lobe (D005625)
Histone Demethylases (D056466)
Behavior (D001519)
Myelin Sheath (D009186)
Chromosomes (D002875)
Biological Products (D001688)
Cell Adhesion (D002448)
Gene Expression (D015870)
X Chromosome Inactivation (D049951)
Adolescent (D000293)
Therapeutics (D013812)
Y Chromosome (D014998)
Angiotensins (D000809)
Prefrontal Cortex (D017397)
Sensitivity and Specificity (D012680)
Tissues (D014024)
Reflex, Righting (D057897)
Memory Disorders (D008569)
Oligodendroglia (D009836)
Gap Junctions (D017629)
Chromatin (D002843)
Histones (D006657)
Anxiety (D001007)
Alcoholism (D000437)
Ethanol (D000431)
Methylation (D008745)
frontal association cortex (MA:0000906)
frontal cortex (MA:0000905)
cell adhesion (GO:0007155)
biological regulation (GO:0065007)
chromatin (GO:0000785)
demethylation (GO:0070988)
methylation (GO:0032259)
righting reflex (GO:0060013)
oligodendrocyte development (GO:0014003)
gap junction (GO:0005921)
developmental process (GO:0032502)
Y chromosome (GO:0000806)
smooth endoplasmic reticulum (GO:0005790)
chromosome (GO:0005694)
demethylase activity (GO:0032451)
histone demethylase activity (GO:0032452)
gap junction assembly (GO:0016264)
gene expression (GO:0010467)
myelination (GO:0042552)
Prediction, detection and recognition (EDAM_operation:2423)
Developmental biology resources (EDAM_topic:3064)
Sequence assembly (EDAM_topic:0196)
Transcriptomics (EDAM_topic:0203)
Molecular biology reference (EDAM_topic:3047)
angiotensin (CHEBI:48433)
Ile(5)-angiotensin II (CHEBI:2719)
dibenz[a,h]anthracene (CHEBI:35299)
(-)-(2R,3R)-2,3-dihydroxybutanamide (CHEBI:28598)
glyceraldehyde 3-phosphate (CHEBI:17138)
advanced glycation end-product (CHEBI:84123)
ribonucleic acid (CHEBI:33697)
perfluorinated compound (CHEBI:134091)
Behavioral abnormality (HP:0000708)
developmental similarity evidence (ECO:0000067)
alcohol abuse (DOID:1574)
anxiety disorder (DOID:2030)
total RNA (EFO:0004964)
anxiety disorder (EFO:0006788)
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)
anatomical junction (UBERON:0007651)
frontal lobe (UBERON:0016525)
anatomical projection (UBERON:0004529)
regulation of gap junction assembly (GO:1903596)

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