GeneSet Information

Tier IV GS408960 • Differentially expressed gene as main effect of treatment (CIE vs Air) and region interaction in brains of C57BL/6J and DBA/2J mice (p < 0.01)_pvalue

DESCRIPTION:

Male C57BL/6J and DBA/2J mice (10 weeks old upon arrival) were purchased from the Jackson Laboratory and assigned to either the air control or CIE group. Mice were allowed to self-administer alcohol (15% v/v vs. water) for 2 h a day (5 days a week) 6 weeks prior to treatment in order to establish baseline consumption. Access to 15% alcohol versus water started 30 min prior to the start of the dark cycle. Following establishment of baseline drinking, two male mice representative of each strain were separated into two groups to be exposed to either weekly cycles of CIE exposure (CIE group) or air control (AIR group) exposure. There was no difference in baseline consumption or preference within strain prior to assignment to AIR or CIE treatment groups (Supplemental Fig. 1). As expected, there was a significant difference in alcohol consumption and preference between strains at baseline (B6 > D2, p < 0.01. Mice assigned to the CIE treatment group were exposed to alcohol vapor for 16 h a day followed by 8 h of withdrawal for 4 days. Following the fourth vapor exposure, mice were given a 72-h abstinence period before resuming ethanol intake in the home cage for 5 days. Mice in the AIR control treatment group were similarly treated but exposed only to air in the inhalation chambers. This pattern of CIE or air control exposure followed by 5 days of ethanol self-administration was repeated for four cycles. A fifth cycle of CIE (or air) exposure followed the fourth ethanol intake evaluation period, and brain tissue was collected 72 h after the last cycle ended. Poly-A enriched mRNA was sequenced on two platforms, ABI SOLID 550XL Wildfire (65 samples) and Ion Proton (39 samples). Differential gene expression was determined using the glm function in R where gene expression (Y) is dependent on treatment, strain, region, and treatment interactions with strain and region: Y ∼ Treatment + Strain + Region + Treatment*Strain + Treatment*Region. Treatment was coded as 0 for AIR and 1 for CIE, 0 for B6 and 1 for D2. Regions were collapsed into three groups based on PCA clustering and coded as 0 for hippocampus (CA1 and CA3 regions), 1 for cortex (Prl, ILC, and VCX), and 2 for the remaining subcortical and limbic and mesolimbic tissue (VTA, NAc, NAs, DMS, CeA, and BST).

LABEL:

DEG effect of treatment (CIE vs Air) x region interaction C57BL/6J and DBA/2J brains (p < 0.01)_pvalue

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

60

DATE ADDED:

2024-08-14

DATE UPDATED:

2025-04-15

SPECIES:

AUTHORS:

Megan K Mulligan, Khyobeni Mozhui, Ashutosh K Pandey, Maren L Smith, Suzhen Gong, Jesse Ingels, Michael F Miles, Marcelo F Lopez, Lu Lu, Robert W Williams

TITLE:

Genetic divergence in the transcriptional engram of chronic alcohol abuse: A laser-capture RNA-seq study of the mouse mesocorticolimbic system.

JOURNAL:

Alcohol (Fayetteville, N.Y.) Feb 2017, Vol 58, pp. 61-72

ABSTRACT:

Genetic factors that influence the transition from initial drinking to dependence remain enigmatic. Recent studies have leveraged chronic intermittent ethanol (CIE) paradigms to measure changes in brain gene expression in a single strain at 0, 8, 72 h, and even 7 days following CIE. We extend these findings using LCM RNA-seq to profile expression in 11 brain regions in two inbred strains - C57BL/6J (B6) and DBA/2J (D2) - 72 h following multiple cycles of ethanol self-administration and CIE. Linear models identified differential expression based on treatment, region, strain, or interactions with treatment. Nearly 40% of genes showed a robust effect (FDR < 0.01) of region, and hippocampus CA1, cortex, bed nucleus stria terminalis, and nucleus accumbens core had the highest number of differentially expressed genes after treatment. Another 8% of differentially expressed genes demonstrated a robust effect of strain. As expected, based on similar studies in B6, treatment had a much smaller impact on expression; only 72 genes (p < 0.01) are modulated by treatment (independent of region or strain). Strikingly, many more genes (415) show a strain-specific and largely opposite response to treatment and are enriched in processes related to RNA metabolism, transcription factor activity, and mitochondrial function. Over 3 times as many changes in gene expression were detected in D2 compared to B6, and weighted gene co-expression network analysis (WGCNA) module comparison identified more modules enriched for treatment effects in D2. Substantial strain differences exist in the temporal pattern of transcriptional neuroadaptation to CIE, and these may drive individual differences in risk of addiction following excessive alcohol consumption. PUBMED: 27894806
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Annotation Information

No sequence read archive data associated with this GeneSet.


Laboratories (D007753)
Drinking (D004326)
Individuality (D007206)
Divorce (D004243)
Economics (D004467)
Alcohol Drinking (D000428)
Gene Expression (D015870)
RNA, Messenger (D012333)
Linear Models (D016014)
Therapeutics (D013812)
Weights and Measures (D014894)
Inhalation (D001239)
Tissues (D014024)
Nucleus Accumbens (D009714)
Transcription Factors (D014157)
Protons (D011522)
Passive Cutaneous Anaphylaxis (D010323)
Organization and Administration (D009934)
Sprains and Strains (D013180)
Aftercare (D000359)
Ethanol (D000431)
Metabolism (D008660)
Hippocampus (D006624)
Cluster Analysis (D016000)
accumbens nucleus (MA:0000892)
hippocampus CA1 (MA:0000950)
hippocampus (MA:0000191)
addiction (MP:0002555)
metabolic process (GO:0008152)
transcription, DNA-dependent (GO:0006351)
RNA metabolic process (GO:0016070)
viral nucleocapsid (GO:0019013)
nascent polypeptide-associated complex (GO:0005854)
transcription factor activity (GO:0003700)
gene expression (GO:0010467)
Pathway or network (EDAM_data:2600)
Transcriptomics (EDAM_topic:0203)
Transcription (EDAM_topic:0110)
Pathways, networks and models (EDAM_topic:0602)
N-acetyl-L-cysteine (CHEBI:28939)
Prolactin (CHEBI:81580)
dibenz[a,h]anthracene (CHEBI:35299)
(-)-(2R,3R)-2,3-dihydroxybutanamide (CHEBI:28598)
dimethyl sulfate (CHEBI:59050)
maleate(2-) (CHEBI:30780)
phenazine-1-carboxylate (CHEBI:62248)
pyrrole-2-carboxylic acid (CHEBI:36751)
ribonucleic acid (CHEBI:33697)
messenger RNA (CHEBI:33699)
atomic nucleus (CHEBI:33252)
dimethyl sulfide (CHEBI:17437)
Mitochondrial inheritance (HP:0001427)
cap analysis of gene expression evidence (ECO:0000309)
non-traceable author statement used in manual assertion (ECO:0000303)
lymphocytic choriomeningitis (DOID:12155)
primary cutaneous amyloidosis (DOID:0050639)
cap analysis gene expression (EFO:0004181)
Mantle cell lymphoma (EFO:1001469)
individual (EFO:0000542)
treatment (EFO:0000727)
obsolete_accumbens nucleus (EFO:0000906)
transcription profiling by high throughput sequencing (EFO:0002770)
alcohol drinking (EFO:0004329)
neonatal abstinence syndrome (EFO:0005799)
RNA-seq assay (MMO:0000659)
core of nucleus accumbens (UBERON:0012170)
terminal nerve (UBERON:0002924)
archicortex (UBERON:0002961)
stria terminalis (UBERON:0003029)
CA3 field of hippocampus (UBERON:0003883)
CA1 field of hippocampus (UBERON:0003881)
Ammon's horn (UBERON:0001954)
posterior communicating artery (UBERON:0001628)
hippocampal formation (UBERON:0002421)
male organism (UBERON:0003101)
neural nucleus (UBERON:0000125)
ventral tegmental area (UBERON:0002691)
caudal intralaminar nuclear group (UBERON:0019295)
bed nucleus of stria terminalis (UBERON:0001880)
nucleus accumbens (UBERON:0001882)
stria of neuraxis (UBERON:0013199)
anatomical projection (UBERON:0004529)
adult cerebral ganglion (UBERON:6110636)
DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)

Gene List • 60 Genes

Genes in threshold: 60

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