Nicotine, acting through the neuronal
nicotinic acetylcholine receptors (nAChRs), can induce
seizures in mice. We aimed to study brain transcriptional response to seizure and to identify genes whose expression is altered after
nicotine-induced
seizures. Whole brains of untreated mice were compared with brains 1 h after seizure activity, using Affymetrix U74Av2 microarrays. Experimental groups included wild-type mice and both
nicotine-induced seizure-sensitive and -resistant nAChR mutant mice. Each genotype group received different
nicotine doses to generate
seizures. This approach allowed the identification of significantly changed genes whose expression was dependent on seizure activity,
nicotine administration, or both but not on the type of nAChR subunit mutation or the amount of
nicotine injected. Significant expression changes were detected in 62 genes (P < 0.05, false discovery rate correction). Among them, gene ontology functional annotation analysis determined that the most significantly overrepresented categories were of genes encoding MAP
kinase phosphatases, regulators of transcription and
nucleosome assembly
proteins. In silico bioinformatic analysis of the promoter regions of the 62 changed genes detected significant enrichments of 16 transcription regulatory elements (TREs), creating a network of transcriptional regulatory responses to
seizures. The TREs for activating
transcription factor and
serum response factor were most significantly enriched, supporting their association with seizure activity. Our data suggest that
nicotine-induced seizure in mice is a useful model to study seizure activity and its global brain transcriptional response. The differentially expressed genes detected here can help us to understand the molecular mechanisms underlying
seizures in animal models and may also serve as candidate genes to study
epilepsy in humans.