Audiogenic seizure as a model of sudden death in epilepsy: A comparative study between four inbred mouse strains from early life to adulthood
Audiogenic seizure as a model of sudden death in epilepsy: A comparative study between four inbred mouse strains from early life to adulthood
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DOI：
10.1111/epi.16432
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发表时间：
2020-01-24
期刊：
影响因子：
5.6
通讯作者：
Biraben, Arnaud
中科院分区：
文献类型：
--
作者：
Martin, Benoit;Dieuset, Gabriel;Biraben, Arnaud
目的：使用听源性癫痫发作（AGS）建立癫痫患者突然意外死亡（SUDEP）的小鼠模型很有价值，因为在没有任何药理或电成分的情况下，声音诱发的癫痫发作后可能会发生死亡。然而，只有少数品系的小鼠容易出现 AGS，并且绝大多数研究涉及 DBA/2 或 DBA/1 近交品系。为了表征 AGS 易感性随年龄的变化，并提供更多可用于 AGS 研究的小鼠，我们对 AGS 反应的变异性进行了比较研究。方法：在两种经典使用的近交系小鼠 DBA/2 和 DBA/1 以及另外两种小鼠品系 BALB/c 和 129/SvTer 中测定了 AGS 随年龄的变化。由于 AGS 刺激的强直性癫痫发作可能是致命的或非致命性的，即使在相同的近交品系中，在第二个实验中，我们研究了 DBA/2J、DBA/1J 和 129/SvTer 小鼠品系中是否存在在强直 AGS 后重现相同反应的先天能力，称为“决定论”。 结果：结果表明 129/SvTer 小鼠是一种更通用的 SUDEP 模型，因为与 DBA/2J 和 DBA/1J 小鼠品系相比，其易感性年龄范围更广。此外，我们发现 AGS 后的 DBA/2J 和 129/SvTer 菌株中的决定论并不总是明显。因此，我们不能确定致命的 AGS 在复苏后的连续测试中总是致命的，反之亦然，在这两种小鼠品系中反之亦然。意义：这些研究强调了不同小鼠品系中 AGS 的表型变异性，显示了另一种小鼠品系 129/SvTer 对于使用 AGS 的研究的价值，从而为 AGS 和 SUDEP 的未来研究提供了有价值的信息。
Objective: Mouse models of sudden unexpected death in epileptic patients (SUDEP) using audiogenic seizures (AGS) are valuable because death can occur following a sound-induced seizure in the absence of any pharmacologic or electric component. However, only a few strains of mice are AGS prone, and the vast majority of studies involve DBA/2 or DBA/1 inbred strains. With the goal of characterizing the variation of AGS susceptibility with age, and of offering a larger panel of mice available for AGS studies, we performed a comparative study of the variability in AGS responses.Methods: The variation of AGS with age was determined in two classically used inbred strains of mice, DBA/2 and DBA/1, and two additional strains, BALB/c and 129/SvTer. As AGS-stimulated tonic seizures can be lethal or nonlethal, even in the same inbred strain, in a second experiment, we addressed whether there is an innate capacity to reproduce the same response after a tonic AGS, referred to as "determinism," in the DBA/2J, DBA/1J, and 129/SvTer mouse strains.Results: Results show that the 129/SvTer mouse is a more versatile model of SUDEP due to its wider age range of susceptibility compared to the DBA/2J and DBA/1J mouse strains. In addition, we show that determinism is not consistently evident in DBA/2J and 129/SvTer strains after AGS. Hence, one cannot be certain that a lethal AGS will always be lethal in successive testing after resuscitation and vice versa in these two mouse strains.Significance: These studies highlight the phenotypic variability of AGS in different mouse strains, show the value of an additional mouse strain, 129/SvTer, for studies using AGS, and thus provide valuable information for future studies of AGS and SUDEP.