Altered auditory-evoked potentials in mice carrying mutated human amyloid presenilin-1 transgenes
Altered auditory-evoked potentials in mice carrying mutated human amyloid presenilin-1 transgenes
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DOI：
10.1016/s0306-4522(02)00714-5
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Tanila, H
中科院分区：
文献类型：
--
作者：
Wang, J;Ikonen, S;Tanila, H
携带人类APPswe和PS1-A264E转基因的转基因小鼠（A/P小鼠）在9月龄左右具有高纤维原性淀粉样蛋白Abeta水平升高（1-42）（A(3)），并形成淀粉样斑块。我们的目的是发现是否可以通过听觉诱发电位的长期记录来检测这些小鼠中β的逐渐积累。A/P双突变小鼠听觉门控受损，皮层N35反应潜伏期增加，但这些变化在7 - 11月龄之间不依赖于年龄。在APP和PS1单突变小鼠的对照实验中，a /P双突变小鼠的听觉门控比APP和PS1小鼠弱。相比之下，与非转基因或PS1小鼠相比，A/P和APP小鼠的N35潜伏期均增加。A/P小鼠Abeta40和Abeta42水平显著升高，APP小鼠Abeta40水平也适度升高。斑块仅在A/P小鼠中沉积。我们得出的结论是，听觉门控受损与Abeta42的过量产生有关，但并不反映其数量。相比之下，N35潜伏期的增加与APP基因型相关，与Abeta42的产生无关。(c) 2003年。Elsevier Science Ltd.出版。版权所有。
Transgenic mice carrying human APPswe and PS1-A264E transgenes (A/P mice) have elevated levels of the highly fibrillogenic amyloid Abeta(1-42) (A(3) and develop amyloid plaques around the age of 9 months. Our aim was to find whether the gradual accumulation of Abeta in these mice can be detected with long-term recording of auditory-evoked potentials. The A/P double-mutant mice had impaired auditory gating and a tendency toward increased latency of the cortical N35 response, but these changes were not age-dependent between 7 and 11 months of age. In a control experiment that included also APP and PS1 single-mutant mice, the A/P double-mutant mice had weaker auditory gating than either APP or PS1 mice. In contrast, increased N35 latency was found in both A/P and APP mice compared with nontransgenic or PS1 mice. The Abeta40 and Abeta42 levels were robustly increased in A/P mice and Abeta40 moderately increased also in APP mice. Plaques were deposited only in A/P mice. We conclude that the impaired auditory gating is associated with the overproduction Abeta42 but does not reflect its amount. In contrast, increased N35 latency is related to the APP genotype independent of Abeta42 production. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.