Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy.
Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy.
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DOI：
10.1016/j.nbd.2010.05.024
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发表时间：
2010-10
影响因子：
6.1
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Huang X;Zhang H;Yang J;Wu J;McMahon J;Lin Y;Cao Z;Gruenthal M;Huang Y
在TSC/PTEN遗传模型中，雷帕霉素抑制mTOR已被证明可抑制癫痫发作。在神经损伤之前或之后立即使用雷帕霉素，也可在获得性模型中防止自发复发性癫痫发作（癫痫发生）的发生。在本研究中，我们在匹罗卡品模型中检测了已经发生慢性自发性癫痫发作的大鼠的mTOR通路。我们发现慢性癫痫大鼠的脑组织中mTOR异常激活。此外，雷帕霉素治疗对mTOR的抑制可显著降低癫痫发作活动。最后，mTOR抑制也显著抑制苔藓纤维的发芽。我们的研究结果表明，通过靶向mTOR通路对某些获得性癫痫进行干预的可能性要大得多。
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.
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影响因子：
5.3
作者：
Borges, K;Gearing, M;Dingledine, R
通讯作者：
Dingledine, R
影响因子：
4.8
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Lenz, G;Avruch, J
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11.2
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