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J Gerontol A Biol Sci Med Sci. 2014 Nov;69(11):1339-52. doi: 10.1093/gerona/glu080. Epub 2014 Jun 3.

Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice.

Author information

1
Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center. zoltan-ungvari@ouhsc.edu.
2
Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center.
3
Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
4
Oklahoma Medical Research Foundation, Arthritis and Clinical Immunology Research Program.
5
Department of Pathophysiology and Gerontology, Medical School and Szentágothai Research Center, University of Pecs, Hungary.
6
Departments of Pediatrics, Anatomy and Cell Biology, New York Medical College-Westchester Medical Center, Valhalla.
7
Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center. Department of Pathophysiology and Gerontology, Medical School and Szentágothai Research Center, University of Pecs, Hungary. Department of Physiology, University of Oklahoma Health Sciences Center. zoltan-ungvari@ouhsc.edu.
8
Donald W. Reynolds Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center. Department of Pathophysiology and Gerontology, Medical School and Szentágothai Research Center, University of Pecs, Hungary. Department of Physiology, University of Oklahoma Health Sciences Center.

Abstract

Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet-fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood-brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging.

KEYWORDS:

Endothelial dysfunction; Learning and memory.; MCI; Vascular cognitive impairment

PMID:
24895269
PMCID:
PMC4204615
DOI:
10.1093/gerona/glu080
[Indexed for MEDLINE]
Free PMC Article

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