Cognitive decline in type 2 diabetic db/db mice may be associated with brain region-specific metabolic disorders

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1863

Article

Zheng, Hong¹  Zheng, Yongquan¹  Zhao, Liangcai¹  Chen, Minjiang¹  Bai, Guanghui²  Hu, Yongsheng¹  Hu, Wenyi¹  Yan, Zhihan²  Gao, Hongchang¹ 

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 2, Dept Radiol, Wenzhou 325027, Peoples R China

关键词: Brain;    Cognition;    Diabetes;    Metabolomics;    Region-specific;    Mixed model;   

DOI  :  10.1016/j.bbadis.2016.11.003

来源: Elsevier

【 摘 要 】

Type 2 diabetes has been associated with cognitive decline, but its metabolic mechanism remains unclear. In the present study, we attempted to investigate brain region-specific metabolic changes in db/db mice with cognitive decline and explore the potential metabolic mechanism linking type 2 diabetes and cognitive decline. We analyzed the metabolic changes in seven brain regions of two types of mice (wild-type mice and db/db mice with cognitive decline) using a H-1 NMR-based metabolomic approach. Then, a mixed-model analysis was used to evaluate the effects of mice type, brain region, and their interaction on metabolic changes. Compared with the wild-type mice, the db/db mice with cognitive decline had significant increases in lactate, glutamine (Gln) and taurine as well as significant decreases in alanine, aspartate, choline, succinate, gamma-Aminobutyric acid (GABA), glutamate (Glu), glycine, N-acetylaspartate, inosine monophosphate, adenosine monophosphate, adenosine diphosphate, and nicotinamide adenine dinucleotide. Brain region-specific metabolic differences were also observed between these two mouse types. In addition, we found significant interaction effects of mice type and brain region on creatine/phosphocreatine, lactate, aspartate, GABA, N-acetylaspartate and taurine. Based on metabolic pathway analysis, the present study suggests that cognitive decline in db/db mice might be linked to a series of brain region-specific metabolic changes, involving an increase in anaerobic glycolysis, a decrease in tricarboxylic acid (TCA) and Gln-Glu/GABA cycles as well as a disturbance in lactate-alanine shuttle and membrane metabolism. (C) 2016 Elsevier B.V. All rights reserved.

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