Strain-and region-specific gene expression profiles in mouse brain in response to chronic nicotine treatment

Abstract

A pathway-focused complementary DNA microarray and gene ontology analysis were used to investigate gene expression profiles in the amygdala, hippocampus, nucleus accumbens, prefrontal cortex (PFC) and ventral tegmental area of C3H/HeJ and C57BL/6J mice receiving nicotine in drinking water (100 μg/ml in 2% saccharin for 2 weeks). A balanced experimental design and rigorous statistical analysis have led to the identification of 3.5-22.1% and 4.1-14.3% of the 638 sequence-verified genes as significantly modulated in the aforementioned brain regions of the C3H/HeJ and C57BL/6J strains, respectively. Comparisons of differential expression among brain tissues showed that only a small number of genes were altered in multiple brain regions, suggesting presence of a brain region-specific transcriptional response to nicotine. Subsequent principal component analysis and Expression Analysis Systematic Explorer analysis showed significant enrichment of biological processes both in C3H/HeJ and C57BL/6J mice, i.e. cell cycle/proliferation, organogenesis and transmission of nerve impulse. Finally, we verified the observed changes in expression using real-time reverse transcriptase polymerase chain reaction for six representative genes in the PFC region, providing an independent replication of our microarray results. Together, this report represents the first comprehensive gene expression profiling investigation of the changes caused by nicotine in brain tissues of the two mouse strains known to exhibit differential behavioral and physiological responses to nicotine.