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Metabolic Brain Disease

, Volume 33, Issue 5, pp 1661–1668 | Cite as

Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a 13C NMR metabolomic study

  • Qi Zhou
  • Hong Zheng
  • Jiuxia Chen
  • Chen Li
  • Yao Du
  • Huanhuan Xia
  • Hongchang Gao
Original Article
  • 84 Downloads

Abstract

Alzheimer’s disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using 13C NMR metabolomics in combination with intravenous [1-13C]-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 13C fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, γ-aminobutyric acid and aspartate) from [1-13C]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the 13C-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.

Keywords

13C flux Energy metabolism Brain glucose Neurodegenerative disease Neurotransmitter 

Abbreviations

AD

Alzheimer’s disease

Ala

Alanine

Asp

Aspartate

13C-NMR

13C nuclear magnetic resonance

GABA

γ-aminobutyric acid

Glu

Glutamate

Gln

Glutamine

Lac

Lactate

MWM

Morris water maze

PC

Pyruvate carboxylase

PDH

Pyruvate dehydrogenase

Suc

Succinate

T1D

Type 1 diabetes

T2D

Type 2 diabetes

TCA

Tricarboxylic acid

WT

Wild-type

Notes

Acknowledgments

The Laboratory Animal Center of Wenzhou Medical University was appreciated for technical services.

Author contributions

HZ and HCG contributed to experimental design. QZ, CL and LCZ contributed to animal feeding and intravenous [1-13C]-glucose infusion, QZ, YD, CL and HHX contributed to sample collection and NMR metabolomic analysis. HZ and HCG contributed to data analysis, result interpretation and writing. All authors have read, revised and approved the final manuscript.

Funding

This study was supported by the National Natural Science Foundation of China (Nos.: 21605115, 21575105) and the Public Welfare Technology Application Research Foundation of Zhejiang Province (No.: 2017C33066).

Compliance with ethical standards

Conflicting interests

The authors declare no conflict of interest in this study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Metabonomics & Medical NMR, School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhouChina

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