Early-life status epilepticus induces long-term deficits in anxiety and spatial learning in mice.

BACKGROUND

One of the most devastating aspects of developmental epilepsy is the long-term impact on behavior. Children with epilepsy show a high co-morbidity with anxiety disorders and autism.

METHODS

To examine whether early-life status epilepticus results in altered anxiety, repetitive behavior, social behavior, and learning and memory, we induced status epilepticus in male C57BL/6 mice on postnatal day (PD) 10. The mice received intraperitoneal injections of either kainic acid (2mg/kg) or 0.9% normal saline. We also included a nontreated control group. Kainic acid induced status epilepticus for approximately 1.5 hrs. At PD60, the adult mice were then tested in a battery of behavioral tasks, including open field activity, elevated-plus maze, light-dark test, marble burying, social chamber, social partition, conditioned fear, novel object recognition, and Morris water maze.

RESULTS

The early-life seizure group showed consistent increases in anxiety in the open field test (p < 0.05), elevated plus maze (p < 0.05), and light-dark task (p < 0.01). The seizure group showed significant (p < 0.01) impairment in the Morris water maze. There were no differences observed in marble burying, social partition, social chamber, novel object recognition, or delay fear conditioning tasks.

CONCLUSIONS

These results demonstrate that a single insult of status epilepticus during the neonatal period is sufficient to cause specific, long-term impairments in anxiety and spatial learning.