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

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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.

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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

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Acknowledgments

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

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).

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Author notes

  1. Qi Zhou and Hong Zheng contributed equally to this work.

Authors and Affiliations

  1. Institute of Metabonomics & Medical NMR, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, China

    Qi Zhou, Hong Zheng, Jiuxia Chen, Chen Li, Yao Du, Huanhuan Xia & Hongchang Gao

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  1. Qi Zhou
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  2. Hong Zheng
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  3. Jiuxia Chen
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  4. Chen Li
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  7. Hongchang Gao
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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.

Corresponding authors

Correspondence to Hong Zheng or Hongchang Gao.

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The authors declare no conflict of interest in this study.

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Zhou, Q., Zheng, H., Chen, J. et al. Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a 13C NMR metabolomic study. Metab Brain Dis 33, 1661–1668 (2018). https://doi.org/10.1007/s11011-018-0274-7

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  • DOI: https://doi.org/10.1007/s11011-018-0274-7

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