Abstracts

Rationale: Autism is a multifactorial childhood disorder that generally involves impairments in social interactions and communication, as well as restricted and repetitive behaviors. The incidence of Autism Spectrum Disorders in the US is about 1 in 150 children. Moreover, about 30% of all individuals with autism develop epilepsy by adulthood. Despite intensive research, no natural animal models of autism and epilepsy are currently available to evaluate etiology and efficacy of therapies. The EL mouse has long been studied as a natural model of multifactorial idiopathic generalized epilepsy. Because epilepsy is a co-morbid trait of autism, we evaluated the EL mouse as a possible natural model of autism. Methods: The neurobiological and behavioral abnormalities previously reported in EL mice were evaluated in light of similar abnormalities previously reported in persons with autism. To validate the EL mouse as a model of autism, we compared the behavior of EL mice (juvenile and adult) to control age-matched DDY mice, a genetically related non-epileptic strain. The mice were compared in the open-field and in the light-dark compartment tests to measure activity, exploratory behavior, and anxiety. Home-cage behavior was also evaluated in EL and DDY mice as a measure of repetitive activity. Results: We show that EL mice, besides developing adolescent-onset seizures, share several neurobiological and behavioral abnormalities with persons with autism. Both EL mice and individuals with autism exhibit increased microglial activation in the cerebellum as well as increased GFAP expression throughout the brain. Furthermore, impairments in social interaction and restricted patterns of interest are evident in both EL mice and persons with autism. Our behavior analysis revealed that basic movement, self-grooming, exploration, and anxiety were significantly (p <0.02) greater in EL mice than in DDY mice. Also, a stereotypic myoclonic jumping behavior was observed in EL mice, but was not seen in DDY mice. Interestingly, seizure activity within twenty-four hours exacerbated the behavioral abnormalities in EL mice. Conclusions: These findings suggest that the EL mouse expresses neurobiological and behavioral abnormalities similar to those seen in persons with autism. We therefore propose that the EL mouse can be utilized as a natural model of both autism and epilepsy.