Abstract

We evaluated the effects of superimposing seizures on a genetic mutation with known involvement in both Autism Spectrum Disorder and in epilepsy. Neuron-subset specific (NS)-Pten heterozygous (HT) and wildtype (WT) adult mice received either intraperitoneal injections of kainic acid (20 mg/kg) to induce status epilepticus or the vehicle (saline). Animals then received a battery of behavioral tasks in order to evaluate activity levels, anxiety, repetitive-stereotyped behavior, social behavior, learning and memory. In the open field task, we found that HT mice after seizures showed a significant increase in total activity and total distance in the surround region of the open field. In the elevated plus maze task, we found that HT mice after seizures displayed increased total distance and velocity as compared to HT mice that did not undergo seizures and WT controls. 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.

Highlights

  • Individuals with a history of seizures have higher incidence rates for other comorbidities

  • Mice that entered into full status epilepticus were included in this study so that all mice fell into the same highest category of seizure severity

  • The most consistent outcome we found in our study was hyperactivity of the Pten haploinsufficient mice that received status epilepticus (SE)

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Summary

Introduction

Individuals with a history of seizures have higher incidence rates for other comorbidities. There is increasing evidence for a strong relationship between epilepsy and autism, with the prevalence of epilepsy in children with autism spectrum disorder (ASD) ranging from 5–40%1–3. In one study with a cohort of almost 15,000 people, approximately 19% of those with epilepsy were found to have ASD, while the controls were only found to have a 2% rate of ASD4. The variety of findings across studies may be due to seizure classification, ASD classification, study populations, and study methods, there is substantial support for the relationship between autism and epilepsy

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