Rapamycin improves social and stereotypic behavior abnormalities induced by neural subset specific Pten deletion.

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In both patients and rodent models, mutations to the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene result in hyperactivation of the mammalian target of rapamycin (mTOR) pathway – a signaling system integral to neural growth – followed by seizures, intellectual disabilities, and autistic behaviors. Rapamycin, an inhibitor of mTOR, can reverse the epileptic phenotype of neural subset specific Pten knockout (NS-Pten KO) mice, but its impact on behavior is not known. To determine the behavioral effects of rapamycin, male and female NS-Pten KO and wildtype (WT) mice were assigned as controls or administered 10 mg/kg of rapamycin for 2 weeks followed by behavioral testing. Rapamycin improved social behavior in both genotypes, p < .05, and stereotypic behaviors in NS-Pten KO mice, p < .05. These data demonstrate the potential clinical use of mTOR inhibitors by showing its administration can reduce the production of autistic-like behaviors in NS-Pten KO mice.

mTOR. Rapamycin. Social behavior. Stereotypic behavior. Seizures. Epilepsy.