Abstracts

Rationale: The immature brain is more prone to seizures and over half of the total cases of prolonged, recurrent seizures (status epilepticus) occur in children less than two years old. Despite this increased neuronal excitability during early development, the effects of seizures during this period produce apparent minor long-tem pathological changes in adulthood, with the exception of deficits in learning and memory. However, there has been little examination of the effects of early-life seizures on anxiety, sensorimotor gating, and in particular social behavior. There is a strong comorbidity between epilepsy and autism, but the link between early-life seizures and later changes in social behavior has not been addressed in animal models. Methods: To address this question we administered kainate (4 mg/kg intraperitoneal) to postnatal day 10 C57/BL6 mice to induce approximately 45-60 minutes of SE. SE was then terminated by pentobarbital (10 mg/kg IP). The parallel control groups consisted of pentobarbital-treated, sham-handled animals and naïve male and female mice. Both male and female mice were included to examine whether there was a gender-specific effect of early-life seizures on behavior. These mice went through a battery of behavioral tests in adulthood: open field activity, elevated-plus maze, social partition, prepulse inhibition, and fear conditioning. Results: The mice with early-life seizures did not show any differences in open-field activity, elevated-plus maze, prepulse inhibition, and fear conditioning compared to control groups. However, the female mice that experienced early-life SE spent much more time at the social partition than the control groups (p < 0.01). This effect was specific to females since males that had experienced early-life SE did not show this effect. Conclusions: This study demonstrates that early-life seizures significantly alter social behavior in female mice but not in male mice without changes in activity, anxiety, sensorimotor gating, or learning and memory. This study provides evidence that early-life seizures may alter social behavior and this effect selectively occurs in females.