Chan Jianxiong, Jones Nigel C, Bush Ashley I, O'Brien Terence J, Kwan Patrick
Department of Medicine (RMH), The University of Melbourne, Parkville, Victoria, Australia.
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Epilepsia. 2015 Jun;56(6):e73-7. doi: 10.1111/epi.12993. Epub 2015 Apr 16.
People with Alzheimer's disease (AD) are up to 10 times more likely to develop epilepsy than the age-matched general population. However, given that only a proportion of patients with AD develop epilepsy, it is likely that additional factors may be required for the epilepsy to emerge. This study aimed to better understand the relationship between AD pathology and seizure susceptibility. It also aimed to investigate a "two-hit" hypothesis for seizure susceptibility through amygdala kindling of rodent AD models. Aged AD mice (Tg2576 model) and wild-type (WT) mice underwent electrical amygdala kindling. Compared with WT mice, Tg2576 mice had significantly lower afterdischarge threshold. Significantly fewer stimulations were required for the Tg2576 mice to reach the first class V seizure. Higher death rate was observed with Tg2576 mice in the kindling group. Both sham and kindled Tg2576 animals had increased levels of sprouting in the supragranular layer of the dentate gyrus compared with the WT counterparts. These findings support the "two-hit" hypothesis and represent a potentially novel research model to help better understand the relationship between AD pathology and epilepsy.
患有阿尔茨海默病（AD）的人患癫痫的可能性比年龄匹配的普通人群高出10倍。然而，鉴于只有一部分AD患者会患上癫痫，癫痫的出现可能还需要其他因素。本研究旨在更好地理解AD病理学与癫痫易感性之间的关系。它还旨在通过对啮齿动物AD模型进行杏仁核点燃来研究癫痫易感性的“双打击”假说。对老年AD小鼠（Tg2576模型）和野生型（WT）小鼠进行了杏仁核电点燃。与WT小鼠相比，Tg2576小鼠的后放电阈值显著更低。Tg2576小鼠达到首次V级癫痫发作所需的刺激次数明显更少。在点燃组中，观察到Tg2576小鼠的死亡率更高。与WT小鼠相比，假手术和点燃的Tg2576动物齿状回颗粒上层的发芽水平均有所增加。这些发现支持了“双打击”假说，并代表了一种潜在的新型研究模型，有助于更好地理解AD病理学与癫痫之间的关系。
