title: Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline.
abstract: BACKGROUND
  Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear. In this study, (1)H nuclear magnetic resonance-based metabonomics and immunohistochemistry was used to explore key metabolic alterations in hippocampus of type 2 diabetic db/db mice with cognition decline in order to advance understanding of mechanisms underlying the pathogenesis of the disease.
  
  
  RESULTS
  Metabonomics reveals that lactate level was significantly increased in hippocampus of db/db mice with cognition decline compared with age-matched wild-type mice. Several tricarboxylic acid cycle intermediates including succinate and citrate were reduced in hippocampus of db/db mice with cognition decline. Moreover, an increase in glutamine level and a decrease in glutamate and γ-aminobutyric acid levels were observed in db/db mice. Results from immunohistochemistry analysis show that glutamine synthetase was increased and glutaminase and glutamate decarboxylase were decreased in db/db mice.
  
  
  CONCLUSIONS
  Our results suggest that the development of diabetes-associated cognition decline in db/db mice is most likely implicated in a reduction in energy metabolism and a disturbance of glutamate-glutamine shuttling between neurons and astrocytes in hippocampus.
authors.affiliation: Radiology Department of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.|School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Radiology Department of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. zhaoliangcai@wmu.edu.cn.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. gaohc27@wmu.edu.cn.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D003071:Cognition; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D016002:Discriminant Analysis; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D016018:Least-Squares Analysis; D008297:Male; D018782:Maze Learning; D008568:Memory; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D066244:Proton Magnetic Resonance Spectroscopy; D014020:Tissue Extracts
chemical_list: D014020:Tissue Extracts; D005973:Glutamine; D018698:Glutamic Acid
keywords: Diabetes-associated cognition decline; Glutamate-glutamine cycle; Metabonomics; Nuclear magnetic resonance