Environmental enrichment improves behavioral outcome in the AY-9944 model of childhood atypical absence epilepsy.

Atypical absence seizures are drug resistant in the majority of children with Lennox-Gastaut syndrome and herald a poor neurodevelopmental outcome. Here we studied the effects of environmental enrichment, enriched housing conditions designed to stimulate sensory and motor systems in the brain, on behavioral outcome in mice treated with the cholesterol biosynthesis inhibitor AY-9944 (AY), a clinically relevant model of atypical absence epilepsy. Beginning at postnatal day (P) 2, C3H mice were treated with AY (7.5 mg/kg) every 6 days until P20 and then weaned into enriched or standard cages. After 30 days (∼P50), AY mice from the enriched housing condition exhibited less behavioral hyperactivity and anxiety, improved olfactory recognition, and spatial learning, but no significant reduction in the number of ictal discharges in comparison with their non-enriched cohorts. The beneficial effects of environmental enrichment in AY model were in some behavioral tests gender-specific in favor of males suggesting that other, possibly hormonally mediated mechanisms, may interact with the therapeutic effects of enrichment. Taken together, these data provide a starting point to derive clinical occupational therapies for improving behavioral outcome in cases of intractable childhood seizures.