Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus.
Lovastatin modulates glycogen synthase kinase-3β pathway and inhibits mossy fiber sprouting after pilocarpine-induced status epilepticus.
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DOI：
10.1371/journal.pone.0038789
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liou HH
中科院分区：
文献类型：
--
作者：
Lee CY;Jaw T;Tseng HC;Chen IC;Liou HH
本实验旨在观察洛伐他汀对癫痫大鼠糖原合成酶激酶3β (GSK-3β)和坍缩反应介质蛋白-2 （CRMP-2）信号通路及苔藓纤维发芽（MFS）的影响。齿状回（DG） MFS是颞叶癫痫（TLE）的重要特征，与自发性复发发作的严重程度和频率高度相关。然而，MFS的分子机制尚不清楚。GSK-3β和CRMP-2是海马中负责轴突生长和神经元极性的基因，因此该通路是研究MFS的潜在靶点。以匹罗卡品诱导的癫痫持续状态动物模型为研究材料。采用Western blot、组织学和电生理技术作为研究工具。结果显示，癫痫诱导后GSK-3β和CRMP-2的表达水平升高，洛伐他汀逆转了这一作用，并显著降低了海马DG和CA3区的MFS程度。癫痫诱导后GSK-3β和CRMP-2表达水平的改变提示GSK-3β和CRMP-2在MFS和癫痫发生中起重要作用。洛伐他汀逆转GSK-3β和CRMP-2的表达水平表明GSK-3β和CRMP-2可能是洛伐他汀抑制MFS的新机制，为MFS和癫痫发生机制的研究提供了新的治疗靶点和研究方向。
This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis.
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影响因子：
64.8
作者：
GOSHIMA, Y;NAKAMURA, F;STRITTMATTER, SM
通讯作者：
STRITTMATTER, SM
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
影响因子：
2.2
作者：
Longo, BM;Mello, LEAM
通讯作者：
Mello, LEAM
影响因子：
2.9
作者：
McKenney, JM
通讯作者：
McKenney, JM
DOI：
10.1006/bbrc.2002.6424
发表时间：
2002-02-22
影响因子：
3.1
作者：
Bagetta, G;Paoletti, AM;Corasaniti, MT
通讯作者：
Corasaniti, MT