BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy

被引:13
|
作者
Foley, Jeannine [1 ]
Burnham, Veronica [1 ]
Tedoldi, Meghan [2 ]
Danial, Nika N. [2 ]
Yellen, Gary [1 ]
机构
[1] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA
[2] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA
关键词
BAD; Kcna1(-/-); K(v)1.1; metabolic seizure resistance; KETOGENIC DIET; MICE; KV1.1;
D O I
10.1111/epi.13960
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1(-/-) model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1(-/-) and Kcna1(-/-) Bad(-/-) double knockout mice to assess survival and seizure severity. We found that Kcna1(-/-) Bad(-/-) mice outlived Kcna1(-/-) mice by approximately 2 weeks. Kcna1(-/-) Bad(-/-) mice also spent significantly less time in seizure than Kcna1(-/-) mice on P24 and the day of death, showing that Bad KO provides seizure resistance in a genetic model of chronic epilepsy.
引用
收藏
页码:E1 / E4
页数:4
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