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Neurobiology of disease · Oct 2010
Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy.
- Xiaoxing Huang, Hailong Zhang, Jun Yang, Jingfan Wu, John McMahon, Yufan Lin, Zhonglian Cao, Michael Gruenthal, and Yunfei Huang.
- Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.
- Neurobiol. Dis. 2010 Oct 1;40(1):193-9.
AbstractInhibition of mTOR by rapamycin has been shown to suppress seizures in TSC/PTEN genetic models. Rapamycin, when applied immediately before or after a neurological insult, also prevents the development of spontaneous recurrent seizures (epileptogenesis) in an acquired model. In the present study, we examined the mTOR pathway in rats that had already developed chronic spontaneous seizures in a pilocarpine model. We found that mTOR is aberrantly activated in brain tissues from rats with chronic seizures. Furthermore, inhibition of mTOR by rapamycin treatment significantly reduces seizure activity. Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway.(c) 2010 Elsevier Inc. All rights reserved.
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