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.
Expression profiles in the human hippocampus from cocaine addicts and age-matched drug-free control subjects. Cocaine abusers had 151 gene transcripts upregulated, while 91 gene transcripts were downregulated.
Authors:
Mash DC, ffrench-Mullen J, Adi N, Qin Y, Buck A, Pablo J.
Genes altered more than 2-fold (p < 0.05) in the liver of mice treated with ethanol.Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p < 0.05), after adjustment by the Benjamini–Hochberg multiple testing correction; these genes displayed ≥ 2-fold induction or repression.
Authors:
Yin HQ, Kim M, Kim JH, Kong G, Kang KS, Kim HL, Yoon BI, Lee MO, Lee BH
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
Study finds genes that regulate extracellalar matrix modeling by examining expression in the hippocampus of human cocaine abuses. This gene set comprises 54 reported to have shown demonstrated significant fold change during the study. The significance of these fold changes have been reported here as p-values obtained from ANOVA t-test.
Authors:
Mash DC, ffrench-Mullen J, Adi N, Qin Y, Buck A, Pablo J.
Differentially expressed in the Nucleus accumbens following 24 hr continuous 9.5g/kg/day alcohol drinking vs. water drinking in alcohol preferring rats. Estimated BAC in the alcohol exposed group was > 85mg%. The 406 significanlty different probe sets represent 374 uniquely named genes, with most gene expression differences in the range of 1.1-1.3 fold.
Bolus fed rats (6g/kg/body weight, 20% ethanol solution) or rats maintained on an intragatric liquid ethanol diet (13/g/kg/d) for a month were compared with controls. Bolus fed rats were killed 3 or 12 hours post alcohol, with alcohol and blood levels taken. Ethanol fed rats were killed at either peak or trough of the urinary alcohol cycle (UAL). Data set is comparison of the experimental group versus control during peak UAL in hepatocytes.
Authors:
Bardag-Gorce F, Oliva J, Dedes J, Li J, French BA, French SW
Bolus fed rats (6g/kg/body weight, 20% ethanol solution) or rats maintained on an intragatric liquid ethanol diet (13/g/kg/d) for a month were compared with controls. Bolus fed rats were killed 3 or 12 hours post alcohol, with alcohol and blood levels taken. Ethanol fed rats were killed at either peak or trough of the urinary alcohol cycle (UAL). Data set is comparison of the experimental group versus control, 12 hours after ethanol bolus.
Authors:
Bardag-Gorce F, Oliva J, Dedes J, Li J, French BA, French SW
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
These genes are a 1 class SAM significant (1% FDR) in nucleus accumbens (core + shell) for saline treated ("basal") control vs. Fyn KO mice. The list was filtered for an average Sscore >2.0 or <-2.0. Data from Farris and Miles, PLoS One, 2013.
Shows the first 25 up-regulated genes in tumours; among these, we found Defcr4 (defensin-related cryptdin 4), Slc30a2 (a solute carrier specific for zinc transport), Lum (lumican, a member of a small leucine-rich proteoglycan family), Mmp12 (matrix metallopeptidase 12), Igfbp5 (insulin growth factor binding protein 5), Mmp7 (matrix metallopeptidase 7), Nos2 (nitric oxide synthase 2, inducible), S100A8 (S100 calcium binding protein A8 (calgranulin A)) and S100A9 (S100 calcium binding protein A9
Authors:
Femia AP, Luceri C, Toti S, Giannini A, Dolara P, Caderni G
Of the 3100 DEGs modulated by vorinostat treatment in HCT116 cells, 24 were up-regulated and 17 were down-regulated >2-fold. Of the 3509 genes modulated following treatment with LBH589 in HCT116 cells, 92 genes were upregulated and 150 were downregulated >2-fold. The top 15 up- and downregulated genes modulated >2-fold for both vorionostat and LBH589 treatment in HCT116 cells are displayed here.
QTL for morphine antinociception on Chr10 at D10Mit51 (19.52 Mbp , Build 37)
Description:
morphine antinociception spans 0.00 - 44.52 Mbp (NCBI Build 37) on Chr10. 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, Helms ML, O\'Toole LA, Jarvis MW, Hain HS, Mogil JS, Belknap JK
QTL for morphine preference on Chr10 at D10MIT282 (24.33 Mbp , Build 37)
Description:
morphine preference spans 0.00 - 49.33 Mbp (NCBI Build 37) on Chr10. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Berrettini WH, Ferraro TN, Alexander RC, Buchberg AM, Vogel WH
QTL for alcohol preference locus on Chr10 at D10Mit126 (39.43 Mbp , Build 37)
Description:
alcohol preference locus spans 14.43 - 64.43 Mbp (NCBI Build 37) on Chr10. 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 alcohol preference locus on Chr10 at D10Mit126 (39.43 Mbp , Build 37)
Description:
alcohol preference locus spans 14.43 - 64.43 Mbp (NCBI Build 37) on Chr10. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes associated with Homo sapiens that interact with the MeSH term 'Benzalkonium Compounds' (D001548). Incorporates data from 7 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 'kallidin, des-Arg(10)-' (C052787). Incorporates data from 3 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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