A High Fat/Cholesterol Diet Recapitulates Some Alzheimer's Disease-Like Features in Mice: Focus on Hippocampal Mitochondrial Dysfunction.
J Alzheimers Dis
; 82(4): 1619-1633, 2021.
Article
em En
| MEDLINE
| ID: mdl-34219714
ABSTRACT
BACKGROUND:
Ample evidence from clinical and pre-clinical studies suggests mid-life hypercholesterolemia as a risk factor for developing Alzheimer's disease (AD) at a later age. Hypercholesterolemia induced by dietary habits can lead to vascular perturbations that increase the risk of developing sporadic AD.OBJECTIVE:
To investigate the effects of a high fat/cholesterol diet (HFCD) as a risk factor for AD by using a rodent model of AD and its correspondent control (healthy animals).METHODS:
We compared the effect of a HFCD in normal mice (non-transgenic mice, NTg) and the triple transgenic mouse model of AD (3xTgAD). We evaluated cognitive performance in relation to changes in oxidative metabolism and neuron-derived nitric oxide (â¢NO) concentration dynamics in hippocampal slices as well as histochemical staining of markers of the neurovascular unit.RESULTS:
In NTg, the HFCD produced only moderate hypercholesterolemia but significant decline in spatial memory was observed. A tendency for decrease in â¢NO production was accompanied by compromised mitochondrial function with decrease in spare respiratory capacity. In 3xTgAD mice, a robust increase in plasma cholesterol levels with the HFCD did not worsen cognitive performance but did induce compromise of mitochondrial function and significantly decreased â¢NO production. We found increased staining of biomarkers for astrocyte endfeet and endothelial cells in 3xTgAD hippocampi, which was further increased by the HFCD.CONCLUSION:
A short term (8 weeks) intervention with HFCD can produce an AD-like phenotype even in the absence of overt systemic hypercholesterolemia and highlights mitochondrial dysfunction as a link between hypercholesterolemia and sporadic AD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camundongos Transgênicos
/
Colesterol
/
Doença de Alzheimer
/
Dieta Hiperlipídica
/
Hipocampo
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Brasil