| flyingrose66 |
2017-03-18 11:18 |
自动信息发布工具，可以访问君笨笨贴吧看看哟罕见病和孤儿药 ? 进展 市场 政策 人物 公司 会议 首页 ? 罕见病和孤儿药 ? PNAS：失神发作的新型疗法 PNAS：失神发作的新型疗法 来源：生物谷 2014-08-24 13:29 2014年8月21日 讯 /生物谷BIOON/ --韩国研究人员已经成功地揭示了人类大脑的神经网络原理机制，这将为失神发作的潜在治疗方法提供一个重要线索。失神发作被认为由调节钙离子流入的大脑丘脑网状核中T型钙离子通道引起的。这些通道使丘脑网状核神经元形成放电模式，导致神经元进入一种过度受激发状态。为了确定放电模式和失神发作之间的关系，研究人员进行了一项实验使用基因打靶技术剔除T型钙离子通道CaV3.3诱导小鼠失神发作。结果表明，小鼠获得完整的T型钙离子通道基因缺失，进而抑制丘脑网状核放电模式，使得小鼠失神发作的频率增加。此外，研究人员第一次观察到紧张性放电也增加了老鼠失神发作的几率。这项研究首次发现紧张性放电在失神发作的感应中发挥着关键作用，它与现有的假设相矛盾，这对失神发作的治疗研究有重要意义。这项研究有意义的方面是它质疑T型钙离子通道在网状丘脑中的作用，并预计将提供一个重要的理论依据关于理解失神发作的发生机制的作用，而且发展一种治疗失神癫痫的有效方法。（yuyu学院）doi:10.1073/pnas.1408609111PMC:PMID:Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in miceSeung Eun Leea,b,c, Jaekwang Leeb, Charles Latchoumanea, Boyoung Leea, Soo-Jin Ohd, Zahangir Alam Saudd,1, Cheongdahm Parkd, Ning Sune, Eunji Cheongf, Chien-Chang Cheng, Eui-Ju Choic, C. Justin Leeb,d, and Hee-Sup Shina,2Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation of T-type Ca2+ channels in the thalamic reticular nucleus (TRN). TRN bursts are believed to be critical for generation and maintenance of thalamocortical oscillations, leading to the spike-and-wave discharges (SWDs), which are the hallmarks of absence seizures. We observed that the RBDs were completely abolished, whereas tonic firing was significantly increased, in TRN neurons from mice in which the gene for the T-type Ca2+ channel, CaV3.3, was deleted (CaV3.3?/?). Contrary to expectations, there was an increased susceptibility to drug-induced SWDs both in CaV3.3?/? mice and in mice in which the CaV3.3 gene was silenced predominantly in the TRN. CaV3.3?/? mice also showed enhanced inhibitory synaptic drive onto TC neurons. Finally, a double knockout of both CaV3.3 and CaV3.2, which showed complete elimination of burst firing and RBDs in TRN neurons, also displayed enhanced drug-induced SWDs and absence seizures. On the other hand, tonic firing in the TRN was increased in these mice, suggesting that increased tonic firing in the TRN may be sufficient for drug-induced SWD generation in the absence of burst firing. These results call into question the role of burst firing in TRN neurons in the genesis of SWDs, calling for a rethinking of the mechani for absence seizure induction.
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