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
Hippocampus Gene Expression Correlates for NOVEL_ADIST_1 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NOVEL_ADIST_1 measures Open Field Inovel TOTAL locomotion ( cm in 1 hr) in the center 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
Hippocampus Gene Expression Correlates for NOVEL_ADIST_1 measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NOVEL_ADIST_1 measures Open Field Inovel TOTAL locomotion ( cm in 1 hr) in the center 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
Hippocampus Gene Expression Correlates for NOVEL_RATIO measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NOVEL_RATIO measures Novel Open Field - locomotion in the periphery as a function of total locomotion. 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
Whole Brain Gene Expression Correlates for NOVEL_RATIO measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The NOVEL_RATIO measures Novel Open Field - locomotion in the periphery as a function of total locomotion. 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
Hippocampus Gene Expression Correlates for SEN_CHCL_ACOUNT_4 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The SEN_CHCL_ACOUNT_4 measures Cocaine Sensitization - TOTAL locomotion (activity beam breaks) 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
Hippocampus Gene Expression Correlates for SHCOUNT45 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The SHCOUNT45 measures Open Field - locomotion (activity beam breaks) 30-45 min post saline 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
Hippocampus Gene Expression Correlates for ACTI10_SAL measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ACTI10_SAL measures Distance traveled (cm) during the second 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
Hippocampus Gene Expression Correlates for C1HCOUNT15 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The C1HCOUNT15 measures Open Field locomotion 0-15 min post cocaine 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
Hippocampus Gene Expression Correlates for INOVEL_ADIST_1 measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The INOVEL_ADIST_1 measures Open Field Inovel TOTAL locomotion (cm in 1 hr) 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
Hippocampus Gene Expression Correlates for INOVEL_ADIST_1 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The INOVEL_ADIST_1 measures Open Field Inovel TOTAL locomotion (cm in 1 hr) 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
Hippocampus Gene Expression Correlates for NEINCOUNT15 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. 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
Hippocampus Gene Expression Correlates for NEINDIST15 measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. 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
Hippocampus Gene Expression Correlates for NEINDIST15 measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. 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
A list of genes whose transcript abundance in the PFC changed significantly 4 hours after an acute dose of ethanol (1.8 g/kg). This list was generated using Fisher's Combined Probability test to analyze saline vs ethanol S-scores across B6 and D2 inbred strains (n=3) and 27 BXD RI lines (n=1). Statistical significance was determined using 1,000 permutations of S-score data and selecting for probe-sets with q-values < 0.05. Aaron Wolen 5-26-10.
Authors:
Wolen AR, Phillips CA, Langston MA, Putman AH, Vorster PJ, Bruce NA, York TP, Williams RW, Miles MF
QTL for ethanol withdrawal on Chr1 at D1Mit122 (42.42 Mbp , Build 37)
Description:
ethanol withdrawal spans 17.42 - 67.42 Mbp (NCBI Build 37) on Chr1. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for body temperature on Chr1 at D1Ncvs75 (79.87 Mbp , Build 37)
Description:
METH responses for body temperature spans 54.87 - 104.87 Mbp (NCBI Build 37) on Chr1. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Acute nicotine - Nicotine vs. Saline DNA microarray Change in gene expression All the animals received a subcutaneous saline injection once daily for 5 days to habituate them to the injection process. On day 6, animals received a subcutaneous injection of saline or nicotine in saline (2 mg / kg). Animals were killed by cervical dislocation 1, 2, 4, or 6 h following saline or nicotine injection. S-score (significance score) algorithm Change in expression at 6 hours. S-scores (significance score) > / = 2 or < / = -2 consistently in two adjacent time-points from the 1-, 2-, 4- and 6-h time-points. For a comparison between two arrays, an S-score of 2 or ?2 corresponds to a P value of 0.046. (NIF Table ID 339 [192])
Authors:
Chen X, Che Y, Zhang L, Putman AH, Damaj I, Martin BR, Kendler KS, Miles MF
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 'entinostat' (C118739). Incorporates data from 11 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Coumestrol' (D003375). Incorporates data from 6 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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