Neuronal conditional knockout of NRSF decreases vulnerability to seizures induced by pentylenetetrazol in mice  

作　　者：Ming Liu Zhejin Sheng Lei Cai Kai Zhao Yu Tian Jian Fei 

机构地区：[1]Labomtory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, ChineseAcademy of Sciences, Shanghai 200031, China [2]School of Life Sciences and Technology, Ton~i University, Shanghai 200092, China [3]Shanghai Research Center for Model Organisms, Pudong, Shanghai 201203, China [4]State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China [5]Graduate School, Chinese Academy of Sciences, Beijing 100049, China

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第6期476-482,共7页生物化学与生物物理学报（英文版）

摘　　要：Neuron restrictive silencer factor （NRSF）, also known as repressor element-I silencing transcription factor, has been reported to modulate neuronal excitability and acts as endogenous anticonvulsant in kainic acid-induced or kindling-evoked seizure activity. However, whether NRSF functions in pentylenetetrazol （PTZ）-induced seizure ac- tivity has never been studied. To investigate the role of en- dogenous NRSF in the epileptogenesis induced by PTZ, in our experiment, NRSF neuronal conditional knockout mice （NRSF cKO） were adopted, in which NRSF was spe- cifically deleted in neurons by the Cre-loxP system. Seizure threshold for PTZ, including the dose-response convulsions and the threshold dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ that induced clonic and tonic seizures was signifi- cantly higher in NRSF cKO mice compared with the control. Similarly, the median lethal dose （LDso） of PTZ in NRSF cKO mice was also considerably higher than that of the control mice. These results revealed that NRSF cKO mice are of higher resistance to convulsions induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced seizure and provided new evidence for differential pathways in diverse types of seizure.Neuron restrictive silencer factor （NRSF）, also known as repressor element-I silencing transcription factor, has been reported to modulate neuronal excitability and acts as endogenous anticonvulsant in kainic acid-induced or kindling-evoked seizure activity. However, whether NRSF functions in pentylenetetrazol （PTZ）-induced seizure ac- tivity has never been studied. To investigate the role of en- dogenous NRSF in the epileptogenesis induced by PTZ, in our experiment, NRSF neuronal conditional knockout mice （NRSF cKO） were adopted, in which NRSF was spe- cifically deleted in neurons by the Cre-loxP system. Seizure threshold for PTZ, including the dose-response convulsions and the threshold dose, was compared between NRSF cKO and control mice. The threshold dose of PTZ that induced clonic and tonic seizures was signifi- cantly higher in NRSF cKO mice compared with the control. Similarly, the median lethal dose （LDso） of PTZ in NRSF cKO mice was also considerably higher than that of the control mice. These results revealed that NRSF cKO mice are of higher resistance to convulsions induced by PTZ. Our work first demonstrated the function of NRSF in PTZ-induced seizure and provided new evidence for differential pathways in diverse types of seizure.

关 键 词：neuron restrictive silencer factor conditionalknockout PENTYLENETETRAZOL SEIZURE 

分 类 号：Q593.2[生物学—生物化学] TP18[自动化与计算机技术—控制理论与控制工程]