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NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction

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Abstract

Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a 1H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences. In addition, the hippocampus was more susceptible to DM compared with other brain regions in rats. More interestingly, significant interaction effects of DM and brain region were observed on alanine, creatine/creatine-phosphate, lactate, succinate, aspartate, glutamate, glutamine, γ-aminobutyric acid, glycine, choline, N-acetylaspartate, myo-inositol and taurine. Based on metabolic pathway analysis, we speculate that cognitive dysfunction in the STZ-induced diabetic rats may be associated with brain region-specific metabolic alterations involving energy metabolism, neurotransmitters, membrane metabolism and osmoregulation.

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Abbreviations

Ala:

alanine

Asp:

aspartate

Cho:

choline

Cre/PCre:

creatine/phosphocreatine

DM:

diabetes mellitus

GABA:

γ-Aminobutyric acid

Gln:

glutamine

Glu:

glutamate

Gly:

glycine

Lac:

lactate

Myo:

myo-inositol

NAA:

N-acetylaspartate

STZ:

streptozotocin

Suc:

succinate

T1DM:

type 1 diabetes mellitus

T2DM:

type 2 diabetes mellitus

Tau:

taurine

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 21575105, 81501303, 21605115), and the Natural Science Foundation of Zhejiang Province (Nos. LY14H090014, LY15H180010, LY16H180009).

Author contributions

HCG, ZHY and HZ contributed to experimental design. DW, PTX and WYH contributed to animal experiment. HZ, LCZ and GHB contributed to NMR-based metabolomics. HZ and HCG contributed to data analysis, result interpretation and writing. All authors have read, revised and approved the final manuscript.

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Authors and Affiliations

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

    Hong Zheng, Qiuting Lin, Dan Wang, Pengtao Xu, Liangcai Zhao, Wenyi Hu & Hongchang Gao

  2. Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China

    Guanghui Bai & Zhihan Yan

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  1. Hong Zheng
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  2. Qiuting Lin
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Correspondence to Hongchang Gao.

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Hong Zheng and Qiuting Lin contributed equally to this work.

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Zheng, H., Lin, Q., Wang, D. et al. NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction. Metab Brain Dis 32, 585–593 (2017). https://doi.org/10.1007/s11011-016-9949-0

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