Development of Autistic-Like Behavior in C57BL/6 Mice Following Early-Life Seizures
The objective of this study is to investigate the effects of flurothyl-induced seizures in C57BL/6 mice on a single day (postnatal day (PD) 10) compared to a group that receives several seizures across a number of days (PD7-11) during neonatal development, to determine how differences in seizure load can impact neonatal communication and whether the PI3K/Akt/mTOR signaling pathway mediates the deficits in communication. Hippocampal tissue was collected at 1hr., 24hrs., on PD12, and on PD15 following PD10 seizures for use in Western blotting analysis of PI3K/Akt/mTOR pathway proteins. On PD12, pups were tested in an isolation-induced ultrasonic vocalization paradigm to evaluate communication impairments. Ultrasonic vocalization analysis indicated both qualitative and quantitative changes in communication following seizures, with a heavier seizure load leading to greater changes in communication. These results were associated with upregulation of specific PI3K/Akt/mTOR pathway proteins at various timepoints following PD10 seizures. These findings provide insights into the role of seizures in the development of one aspect of autistic-like behavior, namely communication deficits, and indicate that hyperactivity of the PI3K/Akt/mTOR pathway may underlie some of the deficits. These results also contribute to the existing body of evidence indicating that inhibition of the PI3K/Akt/mTOR pathway may serve as a therapeutic target for epilepsy and Autism spectrum disorder.