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PLoS One ; 12(1): e0170450, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28103298

RESUMO

Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites-specifically elevated amounts of ß-C-terminal fragment (ß-CTF) and reduced levels of solubilized amyloid Aß40 and Aß42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Precursor de Proteína beta-Amiloide/genética , Amiloidose/prevenção & controle , Colina O-Acetiltransferase/metabolismo , Colina/administração & dosagem , Suplementos Nutricionais , Hipocampo/metabolismo , Presenilina-1/genética , Doença de Alzheimer/dietoterapia , Precursor de Proteína beta-Amiloide/metabolismo , Amiloidose/patologia , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Camundongos , Camundongos Mutantes , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Neurogênese/efeitos dos fármacos , Gravidez , Presenilina-1/metabolismo
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