Increased seizure threshold and severity in young transgenic CRND8 mice
Increased seizure threshold and severity in young transgenic CRND8 mice
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DOI：
10.1016/j.neulet.2004.05.107
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发表时间：
2004-09-02
影响因子：
2.5
通讯作者：
Hyde, LA
中科院分区：
文献类型：
--
作者：
Del Vecchio, RA;Gold, LH;Hyde, LA
报告显示，阿尔茨海默病（AD）患者表现出高的癫痫样疾病的终生患病率。转基因CRND8 （TgCRDN8）是ad样淀粉样发病机制的小鼠模型，表达人类淀粉样前体蛋白695 （K670N/M671L和V717F）的双突变形式。我们之前报道过，当静脉注射戊四唑（PTZ）时，斑块后TgCRND8小鼠表现出更低的癫痫发作阈值和更严重的癫痫发作类型。在这里，我们现在报告斑块前TgCRND8小鼠也表现出对ptz诱导的癫痫发作的敏感性增加，并且癫痫发作类型比年龄匹配的幼鼠对照组更严重。TgCRND8小鼠在斑块沉积之前和之后的阈值较低和更严重的癫痫类型表明，这种基因型差异可能是由于β -淀粉样蛋白（Abeta）毒性而不是斑块形成。因此，TgCRND8小鼠不仅是β生成和斑块沉积的模型，而且可能对阿尔茨海默病相关癫痫发作也有用。2004爱思唯尔爱尔兰有限公司版权所有。
Reports suggest that Alzheimer's disease (AD) patients show a high life-time prevalence of seizure-like disorders. The transgenic CRND8 (TgCRDN8) is a mouse model of AD-like amyloid pathogenesis that expresses a double-mutant form of human amyloid precursor protein 695 (K670N/M671L and V717F). We have previously reported that post-plaque TgCRND8 mice exhibited a lower threshold to seizure with a more severe seizure type when challenged with pentylenetetrazole (PTZ) intravenously. Here, we now report that pre-plaque TgCRND8 mice also demonstrate an increased sensitivity to PTZ-induced seizures with a more severe seizure type over age-matched littermate controls. A lower threshold and more severe seizure type in TgCRND8 mice prior to and after plaque deposition suggest that this genotype difference may be due to beta-amyloid (Abeta) toxicity rather than plaque formation. Thus, the TgCRND8 mice are not only a model for Abeta production and plaque deposition, but may also be useful for AD associated seizure. (C) 2004 Elsevier Ireland Ltd. All rights reserved.