Endogenous amyloid‐β is necessary for hippocampal synaptic plasticity and memory

Annals of Neurology - Tập 69 Số 5 - Trang 819-830 - 2011
Daniela Puzzo1,2, Lucia Privitera1,2, Mauro Fá1, Agnieszka Staniszewski1, Gakuji Hashimoto1, Fahad Aziz1, Mikako Sakurai1, Elena M. Ribé1, Carol M. Troy1, Marc Mercken3, Sonia S. Jung4, Agostino Palmeri2, Ottavio Arancio1
1Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY
2Department of Physiological Sciences, University of Catania, Catania, Italy
3Janssen Pharmaceutica, Johnson & Johnson Pharmaceutical Research & Development, Beerse, Belgium
4Centocor R&D Inc, Radnor, PA

Tóm tắt

AbstractObjective:The goal of this study was to investigate the role of endogenous amyloid‐β peptide (Aβ) in healthy brain.Methods:Long‐term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique.Results:We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ42, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7‐containing nicotinic acetylcholine receptors, and Aβ42 production.Interpretation:Endogenous Aβ42 is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease. Ann Neurol 2011;

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Annals of Neurology

Tập 69 Số 5

819-830

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