Memory-enhancing effects of secreted forms of the β-amyloid precursor protein in normal and amnestic mice

被引:305
作者
Meziane, H
Dodart, JC
Mathis, C
Little, S
Clemens, J
Paul, SM
Ungerer, A
机构
[1] Univ Strasbourg 1, CNRS, Lab Ethol & Neurobiol, URA 1295, F-67000 Strasbourg, France
[2] Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46285 USA
关键词
D O I
10.1073/pnas.95.21.12683
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secreted forms of the beta-amyloid precursor protein (APP(751)(s) and APP(695)(s)) have potent memory enhancing effects and block learning deficits induced by scopolamine. The memory-enhancing effects of APP(s) were observed over a wide range of extremely low doses (0.05-5,000 pg intracerebroventricularly), blocked by anti-APP(s) antisera, and observed when APP(s) was administered either after the first training session in a visual discrimination or a lever-press learning task or before the acquisition trial in an object recognition task APP(s) had no effect on motor performance or exploratory activity. APP(695)(s) and APP(751)(s) were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APP(s) does not require the Kunitz protease inhibitor domain. These data suggest an important role for APP(s)s on memory processes.
引用
收藏
页码:12683 / 12688
页数:6
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