Febrile seizure in infants underlies endophenotypes of autism spectrum disorder in rats

Background: Febrile seizure (FS), which occurs as a response to fever, is the most common seizure that occurs in infants and young children. FS is usually accompanied by diverse neuropsychiatric symptoms including impaired social behaviors; however, no causative link between FS and autism spectrum disorder (ASD) has yet been established. Here, we provide evidence linking FS occurrence with ASD pathogenesis in rats. Methods We inducted febrile seizures through a mercury vapor lamp using infantile rats (postnatal 11 days). At 3 and 12 weeks after FS induction, we examined behavioral tests and immunostaining to identify the association of ASD-like phenotype development with inflammatory damage. Results We developed an FS juvenile rats model and found ASD-like abnormal behaviors including deficits in social novelty, repetitive behaviors, and hyperlocomotion. In addition, FS model juvenile rats showed enhanced levels of gliosis and inflammation in the hippocampal CA2 region and cerebellum. Furthermore, abnormal levels of social and repetitive behaviors persisted in adults FS model rats. Conclusion These findings suggest that occurrence of FS in infants can cause behavioral endophenotypes of ASD.