期刊
METABOLIC BRAIN DISEASE
卷 33, 期 5, 页码 1661-1668出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11011-018-0274-7
关键词
C-13 flux; Energy metabolism; Brain glucose; Neurodegenerative disease; Neurotransmitter
资金
- National Natural Science Foundation of China [21605115, 21575105]
- Public Welfare Technology Application Research Foundation of Zhejiang Province [2017C33066]
Alzheimer's disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using C-13 NMR metabolomics in combination with intravenous [1-C-13]-glucose infusion in APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found that brain glucose was significantly accumulated in APP/PS1 mice relative to wild-type (WT) mice. Reductions in C-13 fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, gamma-aminobutyric acid and aspartate) from [1-C-13]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the C-13-enrichments of the C3 of alanine were significantly lower and the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than WT mice. Taken together, the development of amyloid pathology could cause a reduction in glucose utilization and further result in decreases in energy and neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.
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