Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy.
Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy.
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DOI：
10.1038/s41598-017-17786-0
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发表时间：
2018-01-09
影响因子：
4.6
通讯作者：
Escayg A
中科院分区：
文献类型：
--
作者：
Wong JC;Makinson CD;Lamar T;Cheng Q;Wingard JC;Terwilliger EF;Escayg A
We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy. Using a small-hairpin-interfering RNA directed against the Scn8a gene, we selectively reduced Scn8a expression in the hippocampus of the intrahippocampal kainic acid (KA) mouse model of mesial temporal lobe epilepsy. We found that Scn8a knockdown prevented the development of spontaneous seizures in 9/10 mice, ameliorated KA-induced hyperactivity, and reduced reactive gliosis. These results support the potential of selectively targeting Scn8a for the treatment of refractory epilepsy.
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影响因子：
5.3
作者：
Garg, Saurabh K.;Lioy, Daniel T.;Mandel, Gail
通讯作者：
Mandel, Gail
在白蛋白中间神经元中SCN1a的优先失活会增加癫痫发作的敏感性。
影响因子：
6.1
作者：
Dutton SB;Makinson CD;Papale LA;Shankar A;Balakrishnan B;Nakazawa K;Escayg A
通讯作者：
Escayg A
影响因子：
5.6
作者：
Brodie, MJ;Shorvon, SD;Wolf, P
通讯作者：
Wolf, P
影响因子：
5.6
作者：
LIEB, JP;BABB, TL;ENGEL, J
通讯作者：
ENGEL, J
SCN8A（NAV1.6）的新型从头突变中具有增强的癫痫性脑病儿童的通道激活。
影响因子：
6.1
作者：
Estacion M;O'Brien JE;Conravey A;Hammer MF;Waxman SG;Dib-Hajj SD;Meisler MH
通讯作者：
Meisler MH