Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy

被引：227

作者：

Huang, Xiaoxing ^{[1
]}

Zhang, Hailong ^{[1
]}

Yang, Jun ^{[1
]}

Wu, Jingfan ^{[1
]}

McMahon, John ^{[1
]}

Lin, Yufan ^{[1
]}

Cao, Zhonglian ^{[1
]}

Gruenthal, Michael ^{[2
]}

Huang, Yunfei ^{[1
]}

机构：

[1] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA

[2] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA

来源：

NEUROBIOLOGY OF DISEASE | 2010年 / 40卷 / 01期

关键词：

mTOR; Rapamycin; Chronic seizure; Acquired epilepsy; Mossy fiber sprouting; TUBEROUS SCLEROSIS COMPLEX; INDUCED STATUS EPILEPTICUS; NMDA RECEPTOR ACTIVATION; TEMPORAL-LOBE EPILEPSY; KETOGENIC DIET; MTOR PATHWAY; KAINIC ACID; MOUSE MODEL; BRAIN; EPILEPTOGENESIS;

D O I：

10.1016/j.nbd.2010.05.024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Inhibition 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.

引用

页码：193 / 199

页数：7

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