Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions.
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.
Kimpel
Mark W
MW
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA. mkimpel@iupui.edu
Strother
Wendy N
WN
McClintick
Jeanette N
JN
Carr
Lucinda G
LG
Liang
Tiebing
T
Edenberg
Howard J
HJ
McBride
William J
WJ
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000679:Amygdala / Q000737:chemistry; D000818:Animals; D001923:Brain Chemistry; D002421:Caudate Nucleus / Q000737:chemistry; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000737:chemistry; D016014:Linear Models; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D009714:Nucleus Accumbens / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D011699:Putamen / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009419:Nerve Tissue Proteins