title: NMR-based metabolomics reveals brain region-specific metabolic alterations in streptozotocin-induced diabetic rats with cognitive dysfunction.
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 a1H 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.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Pengtao
authors.initials: P
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Hu
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Bai
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. gaohc27@wmu.edu.cn.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000523:psychology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D017207:Rats, Sprague-Dawley
keywords: Brain metabolism; Cognitive decline; Diabetes mellitus; Hippocampus; Neurotransmitter