Inhibition of the mammalian target of rapamycin blocks epilepsy progression in NS-Pten conditional knockout mice

Autor: Anne E. Anderson, C. Nicole Sunnen, Fabiola Vanegas, Deena Parghi, Joaquin N. Lugo, Gabriella D'Arcangelo, Eric Turcios, Amy L. Brewster, Shivani Mukhi
Rok vydání: 2011
Předmět:
Zdroj: Epilepsia. 52:2065-2075
ISSN: 0013-9580
DOI: 10.1111/j.1528-1167.2011.03280.x
Popis: SUMMARY Purpose: Increased activity of mTOR Complex 1 (mTORC1) has been demonstrated in cortical dysplasia andtuberoussclerosiscomplex,aswellasinanimalmodels of epilepsy. Recent studies in such models revealed that inhibitingmTORC1withrapamycineffectivelysuppressed seizure activity. However, seizures can recur after treatment cessation, and continuous rapamycin exposure can adverselyaffectanimalgrowthandhealth.Here,weevaluated the efficacy of an intermittent rapamycin treatment protocol on epilepsy progression using neuron subset-specific-Pten(NS-Pten)conditionalknockoutmice. Methods: NS-Pten knockouts were treated with a single course of rapamycin during postnatal weeks 4 and 5, or intermittently over a period of 5 months. Epileptiform activity was monitored using video‐electroencephalography (EEG) recordings, and mossy fiber sprouting was evaluated using Timm staining. Survival and body weight were assessed in parallel.
Databáze: OpenAIRE