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NMR-based metabolomics characterizes metabolic changes in different brain regions of streptozotocin-induced diabetic mice with cognitive decline

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Abstract

Diabetes at advanced age increases rise of cognitive impairment, but its potential mechanisms are still far from being fully understood. In this study, we analyzed the metabolic alterations in six different brain regions between streptozotocin (STZ)-induced diabetic mice with cognitive decline (DM) and age-matched controls (CON) using a 1H NMR-based metabolomics approach, to explore potential metabolic mechanisms underlying diabetes-induced cognitive decline. The results show that DM mice had a peculiar metabolic phenotype in all brain regions, mainly involving increased lactate level, decreased choline and energy metabolism as well as disrupted astrocyte-neuron metabolism. Furthermore, these metabolic changes exhibited a brain region-specific pattern. Collectively, our results suggest that brain region-specific metabolic disorders may be responsible for diabetes-induced cognitive dysfunction.

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Abbreviations

T1D:

type 1 diabetes

CON:

normal mice

DM:

diabetes mellitus

STZ:

streptozotocin

MWM:

Morris water maze

Ala:

alanine

ADP:

adenosine diphosphate

AMP:

adenosine monophosphate

Asp:

aspartate

Cho:

choline

Cre:

creatine

Fum:

fumarate

GABA:

γ -aminobutyric acid

Gln:

glutamine

Glu:

glutamate

Gly:

glycine

IMP:

inosine monophosphate

Ino:

inosine

Lac:

lactate

Myo:

myo-inositol

NAA:

N-acetylaspartate

GPC:

glycerophosphorylcholine

Tau:

taurine

Cor:

cortex

Cer:

cerebellum

Hip:

hippocampus

Hyp:

hypothalamus

Mid:

midbrain

Str:

striatum

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Funding

This study was supported by the National Natural Science Foundation of China (Nos.: 21605115 and 81771386), Health Foundation for Creative Talents in Zhejiang Province (2016), Project Foundation for the College Young and Middle-aged Academic Leader of Zhejiang Province (2017) and Wenzhou Bureau of Science and Technology (No.: Y20150087).

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Author notes

  1. Tingting Zhang and Hong Zheng contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China

    Tingting Zhang, Nengzhi Xia, Jiance Li & Yunjun Yang

  2. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China

    Hong Zheng, Kai Fan, Changwei Yang & Hongchang Gao

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  1. Tingting Zhang
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  2. Hong Zheng
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  3. Kai Fan
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  5. Jiance Li
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  6. Changwei Yang
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  7. Hongchang Gao
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Contributions

YJY, HZ and HCG contributed to the experimental design. TTZ, KF and NZX contributed to animal experiments. TTZ, KF, JCL and CWY contributed to the sample collection and NMR metabolomic analysis. HZ and HCG contributed to the data analysis, result interpretation and writing. All authors have read, revised and approved the final manuscript.

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Correspondence to Hongchang Gao or Yunjun Yang.

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Zhang, T., Zheng, H., Fan, K. et al. NMR-based metabolomics characterizes metabolic changes in different brain regions of streptozotocin-induced diabetic mice with cognitive decline. Metab Brain Dis 35, 1165–1173 (2020). https://doi.org/10.1007/s11011-020-00598-z

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