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

被引:142
作者
Tucsek, Zsuzsanna [1 ]
Toth, Peter [1 ]
Tarantini, Stefano [1 ]
Sosnowska, Danuta [1 ]
Gautam, Tripti [1 ]
Warrington, Junie P. [1 ,2 ]
Giles, Cory B. [3 ]
Wren, Jonathan D. [3 ]
Koller, Akos [4 ,5 ]
Ballabh, Praveen [6 ,7 ,8 ]
Sonntag, William E. [1 ]
Ungvari, Zoltan [1 ,4 ,5 ,9 ]
Csiszar, Anna [1 ,4 ,5 ,9 ]
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK 73104 USA
[2] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS USA
[3] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK USA
[4] Univ Pecs, Sch Med, Dept Pathophysiol & Gerontol, Pecs, Hungary
[5] Univ Pecs, Szentagothai Res Ctr, Pecs, Hungary
[6] New York Med Coll, Westchester Med Ctr, Dept Pediat, Valhalla, NY 10595 USA
[7] New York Med Coll, Westchester Med Ctr, Dept Anat, Valhalla, NY 10595 USA
[8] New York Med Coll, Westchester Med Ctr, Dept Cell Biol, Valhalla, NY 10595 USA
[9] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA
来源
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2014年 / 69卷 / 11期
基金
匈牙利科学研究基金会;
关键词
Vascular cognitive impairment; MCI; Endothelial dysfunction; Learning and memory; VASCULAR OXIDATIVE STRESS; HIGH-FAT DIET; IMPAIRS ANGIOGENIC CAPACITY; CEREBRAL-BLOOD-FLOW; AGE-RELATED-CHANGES; GROWTH-HORMONE; ADIPOSE-TISSUE; ENDOTHELIAL FUNCTION; OLDER-ADULTS; METABOLIC SYNDROME;
D O I
10.1093/gerona/glu080
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:1339 / 1352
页数:14
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