Univ Rennes, CHU Rennes, Inserm, LTSI (Laboratoire de Traitement du Signal et de l'Image), UMR-1099, F-35000, Rennes, France.
Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S 1085, F-35000, Rennes, France.
Epilepsia. 2020 Feb;61(2):342-349. doi: 10.1111/epi.16432. Epub 2020 Jan 24.
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.
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 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.
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.
使用听觉性惊厥（AGS）的癫痫患者突发性意外死亡（SUDEP）的小鼠模型是有价值的，因为在没有任何药物或电成分的情况下，声音诱导的癫痫发作后可能会导致死亡。然而，只有少数几种小鼠品系易发生 AGS，并且绝大多数研究都涉及 DBA/2 或 DBA/1 近交系。为了描述 AGS 易感性随年龄的变化，并提供更多可用于 AGS 研究的小鼠品系，我们进行了 AGS 反应变异性的比较研究。
在两种经典使用的近交系小鼠，DBA/2 和 DBA/1，以及另外两种品系 BALB/c 和 129/SvTer 中，确定了 AGS 随年龄的变化。由于 AGS 刺激的强直发作即使在同一近交系中也可能是致命的或非致命的，在第二个实验中，我们研究了 DBA/2J、DBA/1J 和 129/SvTer 小鼠品系是否具有在强直 AGS 后重现相同反应的内在能力，称为“确定性”。
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，其易感性的年龄范围更广。此外，我们还表明，在 AGS 后，DBA/2J 和 129/SvTer 品系中并不总是明显存在确定性。因此，在这两个小鼠品系中，不能确定致命的 AGS 在连续测试中总是致命的，反之亦然。
这些研究突出了不同小鼠品系中 AGS 的表型变异性，显示了另一种小鼠品系 129/SvTer 在使用 AGS 的研究中的价值，从而为未来的 AGS 和 SUDEP 研究提供了有价值的信息。
