title: Analysis of neuron-astrocyte metabolic cooperation in the brain of db/db mice with cognitive decline using 13C NMR spectroscopy.
abstract: Type 2 diabetes has been linked to cognitive impairment, but its potential metabolic mechanism is still unclear. The present study aimed to explore neuron-astrocyte metabolic cooperation in the brain of diabetic (db/db, BKS.Cg-m+/+Leprdb/J) mice with cognitive decline using13C NMR technique in combination with intravenous [2-13C]-acetate and [3-13C]-lactate infusions. We found that the13C-enrichment from [2-13C]-acetate into tricarboxylic acid cycle intermediate, succinate, was significantly decreased in db/db mice with cognitive decline compared with wild-type (WT, C57BLKS/J) mice, while an opposite result was obtained after [3-13C]-lactate infusion. Relative to WT mice, db/db mice with cognitive decline had significantly lower13C labeling percentages in neurotransmitters including glutamine, glutamate, and γ-aminobutyric acid after [2-13C]-acetate infusion. However, [3-13C]-lactate resulted in increased13C-enrichments in neurotransmitters in db/db mice with cognitive decline. This may indicate that the disturbance of neurotransmitter metabolism occurred during the development of cognitive decline. In addition, a reduction in13C-labeling of lactate and an increase in gluconeogenesis were found from both labeled infusions in db/db mice with cognitive decline. Therefore, our results suggest that the development of cognitive decline in type 2 diabetes may be implicated to an unbalanced metabolism in neuron-astrocyte cooperation and an enhancement of gluconeogenesis.
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.|Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Cai
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Minjiang
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Deng
authors.affiliation: Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Ye
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China gaohc27@wmu.edu.cn.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000473:pathology*; D002247:Carbon Isotopes; D002952:Citric Acid Cycle / Q000502:physiology; D060825:Cognitive Dysfunction / Q000209:etiology*; D005943:Gluconeogenesis / Q000502:physiology; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism
chemical_list: D002247:Carbon Isotopes; D018377:Neurotransmitter Agents; D019344:Lactic Acid
keywords: 13C NMR; acetate; brain metabolism; cognitive decline; diabetes