High-dose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy.
High-dose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy.
复制标题
DOI：
10.1111/epi.12246
复制
发表时间：
2013-09
期刊：
影响因子：
5.6
通讯作者：
Buckmaster PS
中科院分区：
文献类型：
--
作者：
Heng K;Haney MM;Buckmaster PS
颗粒细胞轴突（苔藓纤维）发芽在颞叶癫痫发生中的作用尚不清楚且存在争议。雷帕霉素抑制苔藓纤维发芽，但其报告的癫痫发作频率的影响是混合的。本研究使用高剂量雷帕霉素更完全地阻断苔藓纤维发芽并测量对癫痫发作频率的影响。用毛果芸香碱处理小鼠以诱导癫痫持续状态。从24小时后开始并持续2个月，给予溶媒或雷帕霉素（10 mg/kg/d）。从癫痫持续状态后1个月开始，对小鼠进行视频监测，每天9小时，持续1个月，以测量自发运动性癫痫发作的频率。在癫痫监测结束时，制备小鼠子集用于解剖分析。苔藓纤维发芽被测量为在Timm染色切片中显示黑色标记的颗粒细胞层和分子层的比例。在经历癫痫持续状态并用溶剂处理的小鼠中出现广泛的苔藓纤维发芽。在雷帕霉素治疗的小鼠中，苔藓纤维发芽几乎被阻断到幼稚对照的水平。在媒介物和雷帕霉素处理的小鼠中，癫痫发作频率相似。这些发现表明苔藓纤维发芽不是小鼠匹罗卡品模型中癫痫发生所必需的。他们还揭示，雷帕霉素在该模型中不具有抗癫痫发作或抗癫痫作用。
The role of granule cell axon (mossy fiber) sprouting in temporal lobe epileptogenesis is unclear and controversial. Rapamycin suppresses mossy fiber sprouting, but its reported effects on seizure frequency are mixed. The present study used high-dose rapamycin to more completely block mossy fiber sprouting and measure the effect on seizure frequency. Mice were treated with pilocarpine to induce status epilepticus. Beginning 24 h later and continuing for 2 months, vehicle or rapamycin (10 mg/kg/d) was administered. Starting 1 month after status epilepticus, mice were video-monitored 9 h/d every day for 1 month to measure the frequency of spontaneous motor seizures. At the end of seizure monitoring, a subset of mice was prepared for anatomical analysis. Mossy fiber sprouting was measured as the proportion of the granule cell layer and molecular layer that displayed black labeling in Timm-stained sections. Extensive mossy fiber sprouting developed in mice that experienced status epilepticus and were treated with vehicle. In rapamycin-treated mice, mossy fiber sprouting was blocked almost to the level of naïve controls. Seizure frequency was similar in vehicle- and rapamycin-treated mice. These findings suggest mossy fiber sprouting is not necessary for epileptogenesis in the mouse pilocarpine model. They also reveal that rapamycin does not have anti-seizure or anti-epileptogenic effects in this model.
登录
查看更多内容
影响因子：
4.3
作者：
Ljungberg, M. Cecilia;Sunnen, C. Nicole;D'Arcangelo, Gabriella
通讯作者：
D'Arcangelo, Gabriella
影响因子：
64.5
作者：
SABATINI, DM;ERDJUMENTBROMAGE, H;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ
DOI：
10.1523/jneurosci.2392-12.2012
发表时间：
2012-11-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
McMahon J;Huang X;Yang J;Komatsu M;Yue Z;Qian J;Zhu X;Huang Y
通讯作者：
Huang Y
DOI：
10.1523/jneurosci.4852-10.2011
发表时间：
2011-02-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Buckmaster PS;Lew FH
通讯作者：
Lew FH