Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 42, Issue 8, Pages 1410-1424Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X211069266
Keywords
Oxygen consumption rate; oxidative phosphorylation; glycolysis; extracellular acidification rate; ATP
Categories
Funding
- National Institutes of Health: National Institute of Neurological Disorders and Stroke [NS094834, NS114286, NS096237]
- National Institute on Aging [AG074489, AG047296, R01AG049821]
- National Institute of General Medical Sciences [NS094834]
- American Heart Association (National Center Scientist Development Grant) [14SDG20490359]
- Greater Southeast Affiliate Predoctoral Fellowship Award [16PRE27790122, 20PRE35211153]
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Mitochondrial and glycolytic energy pathways play a crucial role in regulating vascular function, and aging can affect the energetics of brain microvessels, making them more vulnerable to injury.
Mitochondrial and glycolytic energy pathways regulate the vascular functions. Aging impairs the cerebrovascular function and increases the risk of stroke and cognitive dysfunction. The goal of our study is to characterize the impact of aging on brain microvascular energetics. We measured the oxygen consumption and extracellular acidification rates of freshly isolated brain microvessels (BMVs) from young (2-4 months) and aged (20-22 months) C57Bl/6 male mice. Cellular ATP production in BMVs was predominantly dependent on oxidative phosphorylation (OXPHOS) with glucose as the preferred energy substrate. Aged BMVs exhibit lower ATP production rate with diminished OXPHOS and glycolytic rate accompanied by increased utilization of glutamine. Impairments of glycolysis displayed by aged BMVs included reduced compensatory glycolysis whereas impairments of mitochondrial respiration involved reduction of spare respiratory capacity and proton leak. Aged BMVs showed reduced levels of key glycolysis proteins including glucose transporter 1 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 but normal lactate dehydrogenase activity. Mitochondrial protein levels were mostly unchanged whereas citrate synthase activity was reduced, and glutamate dehydrogenase was increased in aged BMVs. Thus, for the first time, we identified the dominant role of mitochondria in bioenergetics of BMVs and the alterations of the energy pathways that make the aged BMVs vulnerable to injury.
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