Environmental Enrichment Reverses the Impaired Exploratory Behavior and Altered Gene Expression Induced by Early-Life Seizures

Abstract

Behavioral problems, school failure, and memory impairment are common among children with epilepsy. Currently, no effective treatment exists to promote recovery and neuron regeneration after seizures. To investigate the efficacy of environmental enrichment in reversing early-life seizure-induced changes in exploratory behavior and gene expression, we injected postnatal day 20 to 25 rats with kainic acid or saline and placed them either singly in a cage or as a group of eight in an enriched environment for 7 to 10 days. Exploratory behavior was quantified in an open field, and hippocampal gene analysis was performed on oligonucleotide microarrays. Exploratory behavior in kainic acid isolated rats were decreased in open field, whereas kainic acid rats exposed to an enriched environment behaved similarly to controls (n = 37, analysis of variance, P < .001). Correlated with an improvement in behavior, genes involved in synaptic plasticity and memory consolidation, such as Arc, Homer1a, and Egr1, were significantly increased in rats exposed to environmental enrichment. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed our microarray data on select genes. Our results provide an experimental basis for promoting enriching education programs for children with epilepsy.