Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model.
Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model.
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DOI：
10.1155/2014/310146
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发表时间：
2014
影响因子：
3.1
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Kong S;Cheng Z;Liu J;Wang Y
环噻嗪（Cyclothiazide，CTZ）可同时增强谷氨酸受体的兴奋和抑制GABAA受体的抑制，从而引起海马神经元癫痫样活动。它还被证明可以在自由活动的大鼠中急性诱导癫痫发作行为。然而，CTZ诱导的癫痫大鼠是否可以发展为复发性癫痫仍然是未知的。在目前的研究中，我们证明了46%的CTZ诱导的癫痫大鼠发展为具有复发性癫痫发作行为以及癫痫EEG，其起始潜伏期在2周至数月之间。在CTZ诱导癫痫发作6个月后的慢性癫痫大鼠中，我们的免疫组化结果显示，在所研究的海马CA 1、CA 3和齿状回区，GAD和GAT-1均显著降低。此外，慢性CTZ癫痫大鼠海马BDNF及其受体TrkB也明显减少。结果提示，CTZ诱导的癫痫发作可发展为反复发作，GABA合成和转运的减少以及BDNF-TrkB信号通路的受损可能参与了反复发作的发生。因此，CTZ癫痫大鼠可为癫痫研究和抗惊厥药物试验提供一种新的动物模型。
Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future.
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影响因子：
5.3
作者：
Bai, ZT;Zhao, R;Ji, YH
通讯作者：
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影响因子：
3.6
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Sun Y;Wu Z;Kong S;Jiang D;Pitre A;Wang Y;Chen G
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影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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