Superimposing status epilepticus on NS-PTEN haploinsufficient and wild type mice results in long-term changes in behavior.

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Autism Spectrum Disorder (ASD) is a neurodevelopment disorder with a prevalence rate of approximately 1% in children. Epilepsy is another neurodevelopmental disorder with similar 1% prevalence in the US population. Approximately 1 in 10 individuals will have a seizure within their lifetime. Recent research has shown evidence of a high comorbidity between autism and epilepsy. However, the mechanism underscoring this comorbidity is not well understood. In the present study, we evaluated the effects of superimposing seizures on a genetic mutation (NS-PTEN heterozygous mice) that has been shown to be involved in both autism and epilepsy. We then measured mouse activity levels, anxiety, social behavior, repetitive behavior, and learning in a battery of behavioral tests. NS-PTEN heterozygous (HT) and wildtype (WT) adult mice received injections of kainic acid (20 mg/kg; intraperitoneal) to induce status epilepticus (continuous seizures) or received injections of the vehicle (0.9% physiological saline). They received pentobarbital (20 mg/kg intraperitoneal) to terminate seizures one hour after the first injection, vehicle mice also received the pentobarbital. Following a few days of recovery, they received a battery of behavioral tasks in order to evaluate activity levels, anxiety, repetitive-stereotyped behavior, social behavior, learning and memory. Following the battery of behavioral tests the hippocampus from the mice was collected. A series of western blotting was conducted on the hippocampal samples in order to determine any changes in the PI3K/AKT/mTOR pathway in which PTEN is involved, as well as several synaptic and other related proteins. In the open field task, we found that after seizures HT mice showed a significant increase in total activity and total distance in the surround region of the open field. Following seizures HT mice also displayed increased total distance and velocity as compared to HT mice that did not undergo seizures and WT controls in the elevated plus maze. In the social chamber test, we found the HT mice after seizures displayed an impairment in social behavior. These findings demonstrate that superimposing seizures on a genetic mutation can result in long-term alterations in activity and social behavior in mice.

Autism spectrum disorder. Epilepsy. Learning and memory. Anxiety. Behavior.