Abstracts

Rationale: Autism Spectrum Disorder (ASD) is characterized by changes in repetitive behaviors, social, and communication deficits. One of the leading causes of inherited intellectual disability and a significant genetic contributor to ASD is fragile x syndrome, which occurs through the silencing of the FMR1 gene. There is also a strong relationship between the presence of seizures during early life and the development of autistic-like behaviors. In this study, we investigated the impact of superimposing several seizures on a genetic condition, to determine the impact of seizures, the impact of the genetic condition, the combined impact of both.

Methods: In the present study we investigated the effects of several seizures over many days on the FMR1 knockout (KO) mice. On Postnatal days 7 to 11, we presented flurothyl-induced seizures to wildtype (WT) and FMR1 KO mice. The seizures occurred 3 times a day with two-hour interval between seizures, while the control group received no treatment. A battery of behavioral tests was performed in adult mice (postnatal day 90) to assess the effects of seizures early in life: nose poke, social partition and open field-tested hyperactivity, sociability, anxiety, repetitive and restrictive behavior.

Results: A two-way ANOVA test of our nose poke behavior task revealed that KO mice exhibited both increased consecutive nose pokes, p< .05 and a longer latency to first nose poke, p< .05. Seizure induction increased latency to first nose poke in KO mice, p< .05 compared to KO mice without seizures. In our social behavior task, we found that the mice with early-life seizures had a social behavior deficit compared to controls, p< .05. A two-way ANOVA of the open field task showed that seizures resulted in a decrease in vertical episode count, p< .01, stereotypy time, p< .05 and stereotypic episode count, p< .01. The KO mice displayed an increased number of clockwise revolutions compared to WT, p< .05.