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

Date
2021-11-17
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Abstract

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.

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