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
Cerebellum Gene Expression Correlates for ST_MAX_70 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The ST_MAX_70 measures Maximum startle response to 70 db 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
Cerebellum Gene Expression Correlates for ST_MAX_80 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The ST_MAX_80 measures Maximum startle response to 80 db 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
Cerebellum Gene Expression Correlates for ST_MAX_85 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The ST_MAX_85 measures Maximum startle response to 85 db 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
Hippocampus Gene Expression Correlates for MDMA_ACT_SAL_1 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The MDMA_ACT_SAL_1 measures Locomotor activity of mice on Day 1 under the domain MDMA. 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 associated with bone response to mechanical loading 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (117360795)
QTL associated with bone response to mechanical loading 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (126594840)
Authors:
Kesavan C, Mohan S, Srivastava AK, Kapoor S, Wergedal JE, Yu H, Baylink DJ
QTL associated with P. chabaudi malaria resistance QTL 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (98606078)
Authors:
Longley R, Smith C, Fortin A, Berghout J, McMorran B, Burgio G, Foote S, Gros P
QTL associated with wound healing/regeneration 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (105240821)
Authors:
Heber-Katz E, Leferovich JM, Bedelbaeva K, Gourevitch D
QTL associated with heterogeneity in eye lens protein photooxidation kinetics. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (129076217)
Authors:
Wisser KC, Schauerte JA, Burke DT, Galecki A, Chen S, Miller RA, Gafni A
QTL associated with Immunoregulatory 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (118625692)
Authors:
Puel A, Mevel JC, Bouthillier Y, Decreusefond C, Fridman WH, Feingold N, Mouton D
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