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Endogenous amyloid‐β is necessary for hippocampal synaptic plasticity and memory
Author(s) -
Puzzo Daniela,
Privitera Lucia,
Fa' Mauro,
Staniszewski Agnieszka,
Hashimoto Gakuji,
Aziz Fahad,
Sakurai Mikako,
Ribe Elena M.,
Troy Carol M.,
Mercken Marc,
Jung Sonia S.,
Palmeri Agostino,
Arancio Ottavio
Publication year - 2011
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22313
Subject(s) - long term potentiation , neuroscience , synaptic plasticity , hippocampal formation , endogeny , metaplasticity , hippocampus , psychology , neuronal memory allocation , biology , receptor , endocrinology , biochemistry
Abstract Objective: 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 Aβ 42 , 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 Aβ 42 production. Interpretation: Endogenous Aβ 42 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;