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Aging-related changes in blood-brain barrier integrity and the effect of dietary fat.
Neurodegener Dis 2013; 12(3):125-35ND

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.

Authors+Show Affiliations

Curtin Health Innovation Research Institute, Faculty of Health Science, School of Public Health, Curtin University, Perth, W.A., Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23128303

Citation

Takechi, R, et al. "Aging-related Changes in Blood-brain Barrier Integrity and the Effect of Dietary Fat." Neuro-degenerative Diseases, vol. 12, no. 3, 2013, pp. 125-35.
Takechi R, Pallebage-Gamarallage MM, Lam V, et al. Aging-related changes in blood-brain barrier integrity and the effect of dietary fat. Neurodegener Dis. 2013;12(3):125-35.
Takechi, R., Pallebage-Gamarallage, M. M., Lam, V., Giles, C., & Mamo, J. C. (2013). Aging-related changes in blood-brain barrier integrity and the effect of dietary fat. Neuro-degenerative Diseases, 12(3), pp. 125-35. doi:10.1159/000343211.
Takechi R, et al. Aging-related Changes in Blood-brain Barrier Integrity and the Effect of Dietary Fat. Neurodegener Dis. 2013;12(3):125-35. PubMed PMID: 23128303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aging-related changes in blood-brain barrier integrity and the effect of dietary fat. AU - Takechi,R, AU - Pallebage-Gamarallage,M M, AU - Lam,V, AU - Giles,C, AU - Mamo,J C, Y1 - 2012/11/02/ PY - 2012/02/02/received PY - 2012/09/06/accepted PY - 2012/11/7/entrez PY - 2012/11/7/pubmed PY - 2014/2/22/medline SP - 125 EP - 35 JF - Neuro-degenerative diseases JO - Neurodegener Dis VL - 12 IS - 3 N2 - 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. SN - 1660-2862 UR - https://www.unboundmedicine.com/medline/citation/23128303/Aging_related_changes_in_blood_brain_barrier_integrity_and_the_effect_of_dietary_fat_ L2 - https://www.karger.com?DOI=10.1159/000343211 DB - PRIME DP - Unbound Medicine ER -