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.
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.
Authors:
Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF
Neocortex Gene Expression Correlates for OF_DIST_5_10 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_DIST_5_10 measures Open Field - Total distance traveled 5-10 minutes under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for OF_DIST_5_10 measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The OF_DIST_5_10 measures Open Field - Total distance traveled 5-10 minutes under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Whole Brain Gene Expression Correlates for ACTI20_SAL measured in BXD RI Females obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI20_SAL measures Distance traveled (cm) during the fourth five minute bin after saline under the domain Ethanol. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Cerebellum Gene Expression Correlates for AMCNT15 measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT15 measures Morphine photocell counts minutes 0-15 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for NEINCOUNT15 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEINCOUNT15 measures Novel environment locomotion (activity beam breaks) 0-15 min in the center under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for NEINCOUNT15 measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEINCOUNT15 measures Novel environment locomotion (activity beam breaks) 0-15 min in the center under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for NEINDIST15 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEINDIST15 measures Novel environment locomotion (cm) 0-15 min in the center under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for NEINDIST15 measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The NEINDIST15 measures Novel environment locomotion (cm) 0-15 min in the center under the domain Cocaine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Striatum Gene Expression Correlates for VERCNT45 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The VERCNT45 measures Morphine Vertical Activity 30-45 min under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Striatum Gene Expression Correlates for VERCNT60 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The VERCNT60 measures Morphine vertical activity counts minutes 45-60 under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for nicotine sensitivity on Chr8 at D8Mit124 (13.44 Mbp , Build 37)
Description:
nicotine sensitivity spans 0.00 - 38.44 Mbp (NCBI Build 37) on Chr8. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
alcohol preference spans 0.00 - 40.29 Mbp (NCBI Build 37) on Chr8. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bachmanov AA, Reed DR, Li X, Li S, Beauchamp GK, Tordoff MG
QTL for METH responses for home cage activity on Chr8 at D8Bir2 (25.76 Mbp , Build 37)
Description:
METH responses for home cage activity spans 0.76 - 50.76 Mbp (NCBI Build 37) on Chr8. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
chronic alcohol withdrawal severity spans 1.57 - 51.57 Mbp (NCBI Build 37) on Chr8. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Kyle Warren R, Crabbe JC, Metten P, Gene Erwin V, Belknap JK
None - Basal gene expression profiles between C57BL/6J, DBA/2J, 129P3/J, and SWR/J strains DNA microarray Change in gene expression Two-way analysis of variance (ANOVA). 3,457 probe sets (corresponded to 2,870 different transcripts) with significant inter-strain differences (differ by at least 1.2-fold) - False discovery rate [FDR] < 1%, , rank > 3. Such a large disparity in the mouse striatal transcriptome was estimated by comparing nine array replicates prepared per strain from all of the treatment groups. More than half of the identified probe sets exhibited markedly significant results (1,735 with rank > 7). (NIF Method ID 84.1)
Authors:
Korostynski M, Piechota M, Kaminska D, Solecki W, Przewlocki R
Genes associated with Homo sapiens that interact with the MeSH term 'poly-N-acetyllactosamine' (C037199). Incorporates data from 65 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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