Memory-enhancing effects of secreted forms of the β-amyloid precursor protein in normal and amnestic mice
- *Laboratoire Ethologie et Neurobiologie, Université Louis Pasteur, Unité de Recherche Associée-Centre National de la Recherche Scientifique 1295, 7 rue de l’Université, 67000 Strasbourg, France; and †Neuroscience Discovery Research, Lilly Research Laboratories, Indianapolis, IN 46285
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Communicated by Etienne-Emile Baulieu, College de France, Le Kremlin-Bictre Cedex, France (received for review February 11, 1998)
Abstract
When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secreted forms of the β-amyloid precursor protein (APPs751 and APPs695) have potent memory-enhancing effects and block learning deficits induced by scopolamine. The memory-enhancing effects of APPs were observed over a wide range of extremely low doses (0.05-5,000 pg intracerebroventricularly), blocked by anti-APPs antisera, and observed when APPs 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. APPs had no effect on motor performance or exploratory activity. APPs695 and APPs751 were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APPs does not require the Kunitz protease inhibitor domain. These data suggest an important role for APPss on memory processes.
Footnotes
ABBREVIATIONS
- APP,
- β-amyloid precursor protein;
- APPs,
- secreted form of APP;
- i.c.v.,
- intracerebroventricular;
- RI,
- recognition index;
- NS,
- not significant;
- PKC,
- protein kinase C
- Received February 11, 1998.
- Accepted August 12, 1998.
- Copyright © 1998, The National Academy of Sciences
