The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway

Authors

  • Sharon S. McDaniel,

    1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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  • Nicholas R. Rensing,

    1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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  • Liu Lin Thio,

    1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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  • Kelvin A. Yamada,

    1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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  • Michael Wong

    1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
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Address correspondence to Michael Wong, MD, PhD, Department of Neurology, Washington University School of Medicine PO Box 8111, 660 South Euclid Avenue, St. Louis, MO 63110, U.S.A. E-mail: wong_m@wustl.edu

Summary

The ketogenic diet (KD) is an effective treatment for epilepsy, but its mechanisms of action are poorly understood. We investigated the hypothesis that the KD inhibits mammalian target of rapamycin (mTOR) pathway signaling. The expression of pS6 and pAkt, markers of mTOR pathway activation, was reduced in hippocampus and liver of rats fed KD. In the kainate model of epilepsy, KD blocked the hippocampal pS6 elevation that occurs after status epilepticus. Because mTOR signaling has been implicated in epileptogenesis, these results suggest that the KD may have anticonvulsant or antiepileptogenic actions via mTOR pathway inhibition.

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