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Acta Physiologica 2008; Volume 194, Supplement 665
The 59th National Congress of the Italian Physiological Society
9/17/2008-9/19/2008
Cagliari, Italy
AMYLOID-BETA PEPTIDE MODULATES HIPPOCAMPAL SYNAPTIC PLASTICITY AND MEMORY
Abstract number: P116
PUZZO1,2 D, PRIVITERA1,2 L, LEZNIK2 E, FA'2 M, SAPIENZA1 S, STANISZEWSKI2 A, PALMERI1 A, ARANCIO2 O
1Dept. of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA
2Dept. of Physiological Sciences, University of Catania, Catania, Italy
Aim:
High levels of amyloid-b peptide (Ab) play a major role in Alzheimer's disease causing synaptic dysfunction and memory loss. However, low picomolar amounts of Ab are produced in the healthy brain. The aim of this study was to investigate whether Ab has a physiological function.
Methods:
We performed electrophysiological recordings and behavioural tests on C57/Bl6 and a7-nAchRs knockout mice. Drugs were delivered trough cannulas (intrahippocampal injections).
Results:
Low picomolar levels of human Ab42 enhanced long-term potentiation (LTP) as well as reference and contextual fear memory. The mechanism of action of Ab involved an increase in neurotransmitter release during tetanus as Ab42 enhanced post-tetanic potentiation (PTP). This effect was mediated by a7-nicotinic acetylcholine receptors (a7-nAchRs), since the Ab-induced PTP enhancement was blocked by the nAchR antagonists mecamylamine and a-bungarotoxin and deletion of the a7-nAchRs in knock-out mice. Moreover, picomolar Ab42 failed to enhance LTP as well as memory in mice lacking a7-nAchRs.
Conclusion:
These findings strongly support the hypothesis that Ab modulates synaptic plasticity and memory in the healthy brain. This effect involves activation of a7-nAchRs.
*Supported by NIH Grant NS049442 to O.A. and the Alzheimer's Association grant NIRG-07-59597 to D.P.
To cite this abstract, please use the following information:
Acta Physiologica 2008; Volume 194, Supplement 665 :P116