Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy.
Rapamycin suppresses the recurrent excitatory circuits of dentate gyrus in a mouse model of temporal lobe epilepsy.
复制标题
雷帕霉素抑制颞叶癫痫小鼠模型中齿状回的复发性兴奋回路。
DOI：
10.1016/j.bbrc.2012.02.143
复制
发表时间：
2012
影响因子：
3.1
通讯作者：
B. Xiao
中科院分区：
文献类型：
--
作者：
Haiyun Tang;H. Long;Chang Zeng;Yi Li;Fangfang Bi;Jinhui Wang;Hao Qian;B. Xiao
周期性兴奋回路和异常周期性兴奋性输入对于癫痫发生至关重要。对颞叶癫痫的研究表明，代表突触重组的苔藓纤维发芽导致异常的复发性兴奋回路和输入的形成。哺乳动物雷帕霉素靶蛋白（mTOR）通路最近被证明在苔藓纤维发芽中很重要。在本研究中，将 mTOR 抑制剂雷帕霉素注射到颞叶癫痫小鼠体内。通过全细胞膜片钳、细胞外记录和蒂姆染色研究海马的电生理和组织学特性。癫痫发生后，颗粒细胞中自发性兴奋性突触后电流（EPSC）的频率和逆向诱发EPSC的幅度显着增加，并检测到癫痫样活动和苔藓纤维出芽，这表明异常的反复兴奋回路的形成。通过使用雷帕霉素，自发 EPSC 的频率、逆向诱发 EPSC 的幅度、癫痫样活动和苔藓纤维出芽均被显着抑制。我们的研究结果表明雷帕霉素通过抑制齿状回的周期性兴奋回路而发挥抗癫痫作用。
Recurrent excitatory circuits and abnormal recurrent excitatory inputs are essential in epileptogenesis. Studies in temporal lobe epilepsy have shown that mossy fiber sprouting, which represents synaptic reorganization, renders the formation of abnormal recurrent excitatory circuits and inputs. The mammalian target of rapamycin (mTOR) pathway has recently been proved important in mossy fiber sprouting. In the present study, rapamycin, a mTOR inhibiter, was injected into the mouse of temporal lobe epilepsy. Electrophysiological and histological properties of the hippocampus were investigated by whole cell patch clamp, extracellular recording and Timm staining. Following the development of epilepsy, frequency of spontaneous excitatory postsynaptic currents (EPSCs) and amplitude of antidromically evoked EPSCs in granule cells were remarkably increased, as well as the epileptiform activity and mossy fiber sprouting were detected, which indicated the formation of abnormal recurrent excitatory circuits. By the use of rapamycin, frequency of spontaneous EPSCs, amplitude of antidromically evoked EPSCs, the epileptiform activity and mossy fiber sprouting were all remarkably suppressed. Our findings suggested an anti-epileptogenic role of rapamycin by suppressing the recurrent excitatory circuits of dentate gyrus.
红藻氨酸诱导癫痫大鼠海马切片齿状回中新谷氨酸能通路的生理揭示。
影响因子：
2.5
作者：
Patrylo,PR;Dudek,FE
通讯作者：
Dudek,FE
影响因子：
2.5
作者：
Lynch, M;Sutula, T
通讯作者：
Sutula, T