Abstracts

Rationale: One of the most devastating aspects of developmental epilepsy is the long-term impact on cognitive behavior. In addition, children with epilepsy show a high co-morbidity with psychiatric disorders and autism spectrum disorder (ASD). One of the critical determinants of a child s behavioral outcome in autistic spectrum disorder and cognitive behavior is the age of onset of seizures. Methods: In order to examine whether early-life seizures result in learning and memory deficits and behavioral features of ASD we administered the inhalant fluorothyl to induce seizures in C57BL/6 mice. The mice received three seizures per day for five days starting on postnatal day 7. The parallel control groups consisted of similarly handled animals that were not exposed to fluorothyl, and na ve mice. Male and female mice were both included to examine whether there was a sex-specific effect of early-life seizures on behavior. The subjects were then processed through a battery of behavioral tests in adulthood: open field activity, elevated-plus maze, nose-poke assay, marble burying, social partition, social chamber, and Morris water maze. Results: The mice with early-life seizures had learning and memory deficits in the training portion of the Morris water maze (p < 0.05) and probe trial (p < 0.01). The mice with seizures showed no differences in marble burying, nose-poke assay, open-field or plus-maze testing compared to controls. However, they showed a significant difference in the social chamber and social partition tests. Mice with early-life seizures showed a significant decrease in the total time they spent at the cup with the other mice (p < 0.01) and showed no preference in the mean interaction time with the cage containing the mouse than with the novel object, while the control mice showed a significant preference for the cage with the mouse (p < 0.01). These results were similar in male and female mice. However, male mice with prior seizures did not show an increase preference to the novel mouse in the social partition test compared to the control male mice. Both social behavior tests suggest that early-life seizures result in severe disruptions in social behavior. Conclusions: These results indicate that early-life seizures result in deficits in hippocampal-dependent memory tasks and produce long-term disruptions in social behavior.