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    Aging-Related Changes in Blood-Brain Barrier Integrity and the Effect of Dietary Fat

    189548_189548.pdf (988.9Kb)
    Access Status
    Open access
    Authors
    Takechi, Ryusuke
    Pallebage-Gamarallage, Menuka
    Lam, Virginie
    Giles, Cory
    Mamo, John
    Date
    2012
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Takechi, R. and Pallebage-Gamarallage, M.M. and Lam, V. and Giles, C. and Mamo, J.C. 2012. Aging-Related Changes in Blood-Brain Barrier Integrity and the Effect of Dietary Fat. Neurodegenerative Diseases. 12: pp. 1-11.
    Source Title
    Neurodegenerative
    DOI
    10.1159/000343211
    ISSN
    1660-2854
    Remarks

    Copyright © 2012 S. Karger AG

    URI
    http://hdl.handle.net/20.500.11937/40777
    Collection
    • Curtin Research Publications
    Abstract

    Background: Disturbances in blood-brain barrier (BBB) integrity contribute to the onset and progression of neurodegenerative diseases including Alzheimer’s disease (AD) and vascular dementia (VaD). Aging is positively associated with AD and VaD risk, but this may reflect comorbidities or the effects of other chronic modulators of vascular function such as diet. Objective: To explore putative synergistic effects of aging with diet, in this study genetically unmanipulated mice were maintained on diets enriched in saturated fatty acids (SFA) or cholesterol and compared to mice provided with low-fat (LF) feed formula. Methods: The functional integrity of the BBB was assessed following 3, 6 and 12 months of dietary intervention commenced at 6 weeks of age, by determining the brain parenchymal extravasation of immunoglobulin G (IgG). Results: Mice maintained on the SFA- or cholesterol-enriched diet showed significant parenchymal IgG abundance following 3 months of feeding, concomitant with diminished expression of the tight junction protein occludin. LF control mice had essentially no evidence of BBB disturbances. Six months of SFA feeding exacerbated the difference in IgG abundance compared to the LF mice. At 12 months of feeding, the control LF mice also had significant parenchymal IgG that was comparable to mice fed the SFA- or cholesterol-enriched diet for 3 months. However, there may have been an adaptation to the fat-enriched diets because SFA and cholesterol did not exacerbate IgG parenchymal accumulation beyond 6 months of feeding. Conclusion: Collectively, the study suggests that diets enriched in SFA or cholesterol accelerate the onset of BBB dysfunction that otherwise occurs with aging.

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