Endogenous amyloid-ß is necessary for hippocampal synaptic plasticity and memory.
Ann Neurol
; 69(5): 819-30, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21472769
ABSTRACT
OBJECTIVE:
The goal of this study was to investigate the role of endogenous amyloid-ß peptide (Aß) 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 Aß 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 Aß42, suggesting that endogenously produced Aß is needed for normal LTP and memory. Furthermore, the effect of endogenous Aß on plasticity and memory was likely due to regulation of transmitter release, activation of α7-containing nicotinic acetylcholine receptors, and Aß42 production.INTERPRETATION:
Endogenous Aß42 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 Aß levels to treat Alzheimer disease.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Potenciação de Longa Duração
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Hipocampo
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Memória
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article