Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions

Mark W. Kimpel, Wendy N. Strother, Jeanette McClintick, Lucinda G. Carr, Tiebing Liang, Howard Edenberg, William J. McBride

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P < .05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

Original languageEnglish
Pages (from-to)95-132
Number of pages38
JournalAlcohol
Volume41
Issue number2
DOIs
StatePublished - Mar 2007

Fingerprint

Gene expression
Rats
Brain
brain
Genes
alcohol
Alcohols
Gene Expression
Putamen
Frontal Lobe
Amygdala
regulation
Hippocampus
Cell Death
Cell death
Microarrays
death
Gene Ontology
Neuropeptide Y
Nucleus Accumbens

Keywords

  • Alcohol-non-preferring NP rat
  • Alcohol-preferring P rat
  • Amygdala
  • Caudate-putamen
  • Frontal cortex
  • Gene expression
  • Hippocampus
  • Microarrays
  • Nucleus accumbens

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neuroscience(all)
  • Toxicology
  • Health(social science)

Cite this

Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions. / Kimpel, Mark W.; Strother, Wendy N.; McClintick, Jeanette; Carr, Lucinda G.; Liang, Tiebing; Edenberg, Howard; McBride, William J.

In: Alcohol, Vol. 41, No. 2, 03.2007, p. 95-132.

Research output: Contribution to journalArticle

Kimpel, Mark W. ; Strother, Wendy N. ; McClintick, Jeanette ; Carr, Lucinda G. ; Liang, Tiebing ; Edenberg, Howard ; McBride, William J. / Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions. In: Alcohol. 2007 ; Vol. 41, No. 2. pp. 95-132.
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AU - Kimpel, Mark W.

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AU - Carr, Lucinda G.

AU - Liang, Tiebing

AU - Edenberg, Howard

AU - McBride, William J.

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N2 - The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P < .05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

AB - The objective of this study was to determine if there are innate differences in gene expression in selected CNS regions between inbred alcohol-preferring (iP) and -non-preferring (iNP) rats. Gene expression was determined in the nucleus accumbens (ACB), amygdala (AMYG), frontal cortex (FC), caudate-putamen (CPU), and hippocampus (HIPP) of alcohol-naïve adult male iP and iNP rats, using Affymetrix Rat Genome U34A microarrays (n = 6/strain). Using Linear Modeling for Microarray Analysis with a false discovery rate threshold of 0.1, there were 16 genes with differential expression in the ACB, 54 in the AMYG, 8 in the FC, 24 in the CPU, and 21 in the HIPP. When examining the main effect of strain across regions, 296 genes were differentially expressed. Although the relatively small number of genes found significant within individual regions precluded a powerful analysis for over-represented Gene Ontology categories, the much larger list resulting from the main effect of strain analysis produced 17 over-represented categories (P < .05), including axon guidance, gliogenesis, negative regulation of programmed cell death, regulation of programmed cell death, regulation of synapse structure function, and transmission of nerve impulse. Co-citation analysis and graphing of significant genes revealed a network involved in the neuropeptide Y (NPY) transmitter system. Correlation of all significant genes with those located within previously established rat alcohol QTLs revealed that of the total of 313 significant genes, 71 are located within such QTLs. The many regional and overall gene expression differences between the iP and iNP rat lines may contribute to the divergent alcohol drinking phenotypes of these rats.

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KW - Microarrays

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