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遗传性惊厥在杂交草原田鼠品系中的表现。

Hereditary convulsions in an outbred prairie vole line.

机构信息

University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.

University of Toledo College of Natural Sciences and Mathematics, Toledo, OH 43606, USA.

出版信息

Epilepsy Res. 2023 Sep;195:107202. doi: 10.1016/j.eplepsyres.2023.107202. Epub 2023 Aug 2.

Abstract

Patients with epilepsy are significantly burdened by the disease due to long-term health risks, the severe side effect profiles of anti-epileptic drugs, and the strong possibility of pharmacoresistant refractory seizures. New animal models of epilepsy with unique characteristics promise to further research to address these ongoing problems. Here, we characterize a newly developed line of prairie voles (Microtus ochrogaster, UTol:HIC or "Toledo" line) that presents with a hereditary, adult-onset, handling-induced convulsion phenotype. Toledo voles were bred for four generations and tested to determine whether the observed phenotype was consistent with epileptic seizures. Toledo voles maintained a stable 22 % incidence of convulsions across generations, with an average age of onset of 12-16 weeks. Convulsions in Toledo voles were reliably evoked by rodent seizure screens and were phenotypically consistent with murine seizures. At the colony level, Toledo voles had a 7-fold increase in risk for sudden unexpected death from unknown causes, which parallels sudden unexpected death in epilepsy (SUDEP) in human patients. Finally, convulsions in Toledo voles were reduced or prevented by treatment with the anti-epileptic drug levetiracetam. Taken in combination, these results suggest that convulsions in Toledo voles may be epileptic seizures. The Toledo prairie vole strain may serve as a new rodent model of epilepsy in an undomesticated, outbred species.

摘要

患有癫痫的患者由于长期健康风险、抗癫痫药物严重的副作用以及耐药性难治性癫痫发作的可能性较大,而受到严重影响。具有独特特征的新的癫痫动物模型有望进一步研究以解决这些持续存在的问题。在这里,我们描述了一种新开发的草原田鼠(Microtus ochrogaster,UTol:HIC 或“托莱多”系),它具有遗传性、成年发病、处理诱导性惊厥表型。托莱多田鼠经过四代繁殖并进行测试,以确定观察到的表型是否与癫痫发作一致。托莱多田鼠在各代中保持着稳定的 22%惊厥发生率,平均发病年龄为 12-16 周。通过啮齿动物惊厥筛查可以可靠地诱发托莱多田鼠的惊厥,其表型与小鼠惊厥一致。在群体水平上,托莱多田鼠因未知原因突然意外死亡的风险增加了 7 倍,这与人类患者的癫痫突然意外死亡(SUDEP)相似。最后,用抗癫痫药物左乙拉西坦治疗可减少或预防托莱多田鼠的惊厥。综上所述,这些结果表明托莱多田鼠的惊厥可能是癫痫发作。托莱多草原田鼠品系可能成为一种新的非驯化、杂交物种的癫痫啮齿动物模型。

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