NYMC Faculty Publications

Aging Exacerbates Obesity-Induced Cerebromicrovascular Rarefaction, Neurovascular Uncoupling, and Cognitive Decline in Mice

Author Type(s)

Faculty

DOI

10.1093/gerona/glu080

Journal Title

The Journals of Gerontology

First Page

1339

Last Page

1352

Document Type

Article

Publication Date

11-1-2014

Department

Medicine

Keywords

Aging, Animals, Blood-Brain Barrier, Brain, Cerebrovascular Circulation, Cognition Disorders, Diet, High-Fat, Disease Models, Animal, Hand Strength, Hippocampus, Male, Maze Learning, Mice, Mice, Inbred C57BL, Microvessels, Neovascularization, Physiologic, Obesity, Oxidative Stress, Pericytes, Transcriptome

Disciplines

Medicine and Health Sciences

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.

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