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A High Fat/Choleste...
A High Fat/Cholesterol Diet Recapitulates Some Alzheimers Disease-Like Features in Mice: Focus on Hippocampal Mitochondrial Dysfunction
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- Mancini, Gianni (author)
- Univ Fed Santa Catarina, Brazil
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- Dias, Candida (author)
- Univ Coimbra, Portugal; Univ Coimbra, Portugal
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- Lourenco, Catia F. (author)
- Univ Coimbra, Portugal; Univ Coimbra, Portugal
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- Laranjinha, Joao (author)
- Univ Coimbra, Portugal; Univ Coimbra, Portugal
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- de Bem, Andreza (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Univ Fed Santa Catarina, Brazil; Univ Brasilia, Brazil
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- Ledo, Ana (author)
- Univ Coimbra, Portugal; Univ Coimbra, Portugal
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(creator_code:org_t)
- IOS PRESS, 2021
- 2021
- English.
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In: Journal of Alzheimer's Disease. - : IOS PRESS. - 1387-2877 .- 1875-8908. ; 82:4, s. 1619-1633
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Subject headings
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- Background: Ample evidence from clinical and pre-clinical studies suggests mid-life hypercholesterolemia as a risk factor for developing Alzheimers 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 ((NO)-N-center dot) 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 (NO)-N-center dot 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 (NO)-N-center dot 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimers disease; high fat/cholesterol diet; hippocampus; spare respiratory capacity
Publication and Content Type
- ref (subject category)
- art (subject category)
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