GeneSet Information

Tier IV GS15467 • Ethanol Regulated Genes from Kerns 2005

DESCRIPTION:

A list of the 307 genes found to be upregulated or downregulated by ethanol in PFC, VTA or NA of B6 or D2 mice. ID number represents cluster membership from Figure 4.

LABEL:

EtOH Reg Genes Kerns05

SCORE TYPE:

Effect

DATE ADDED:

2009-02-03

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF

TITLE:

Ethanol-responsive brain region expression networks: implications for behavioral responses to acute ethanol in DBA/2J versus C57BL/6J mice.

JOURNAL:

The Journal of neuroscience : the official journal of the Society for Neuroscience Mar 2005, Vol 25, pp. 2255-66

ABSTRACT:

Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three brain regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanol-regulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was brain region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain region-specific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving. PUBMED: 15745951
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Annotation Information



Social Control, Formal (D012926)
Brain (D001921)
Gene Expression Regulation (D005786)
Animals (D000818)
Species Specificity (D013045)
Reinforcement (Psychology) (D012054)
Behavior (D001519)
Multivariate Analysis (D015999)
Mice (D051379)
Behavior, Animal (D001522)
Quantitative Trait Loci (D040641)
Drug Administration Schedule (D004334)
Microarray Analysis (D046228)
Neurogenesis (D055495)
Central Nervous System Depressants (D002492)
Dopamine (D004298)
Role (D012380)
Computational Biology (D019295)
Neuronal Plasticity (D009473)
Neuropeptides (D009479)
Adaptation, Psychological (D000223)
Reverse Transcriptase Polymerase Chain Reaction (D020133)
Prefrontal Cortex (D017397)
Nucleus Accumbens (D009714)
Ventral Tegmental Area (D017557)
Oligonucleotide Array Sequence Analysis (D020411)
Mice, Inbred C57BL (D008810)
Mice, Inbred DBA (D008811)
Mice, Inbred Strains (D008815)
Methods (D008722)
Brain-Derived Neurotrophic Factor (D019208)
Reward (D012201)
Dose-Response Relationship, Drug (D004305)
Tretinoin (D014212)
Chromatin (D002843)
Injections (D007267)
Blotting, Western (D015153)
Ethanol (D000431)
Genes, Developmental (D050437)
Cluster Analysis (D016000)
brain (MA:0000168)
addiction (MP:0002555)
chromatin (GO:0000785)
neurogenesis (GO:0022008)
sensitization (GO:0046960)
nucleus (GO:0005634)
gene expression (GO:0010467)
signaling (GO:0023052)
myelination (GO:0042552)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351