NMR-based metabolomics characterizes metabolic changes in different brain regions of streptozotocin-induced diabetic mic
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ORIGINAL ARTICLE
NMR-based metabolomics characterizes metabolic changes in different brain regions of streptozotocin-induced diabetic mice with cognitive decline Tingting Zhang 1 & Hong Zheng 2 & Kai Fan 2 & Nengzhi Xia 1 & Jiance Li 1 & Changwei Yang 2 & Hongchang Gao 2 & Yunjun Yang 1 Received: 2 August 2019 / Accepted: 1 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Diabetes at advanced age increases rise of cognitive impairment, but its potential mechanisms are still far from being fully understood. In this study, we analyzed the metabolic alterations in six different brain regions between streptozotocin (STZ)induced diabetic mice with cognitive decline (DM) and age-matched controls (CON) using a 1H NMR-based metabolomics approach, to explore potential metabolic mechanisms underlying diabetes-induced cognitive decline. The results show that DM mice had a peculiar metabolic phenotype in all brain regions, mainly involving increased lactate level, decreased choline and energy metabolism as well as disrupted astrocyte-neuron metabolism. Furthermore, these metabolic changes exhibited a brain region-specific pattern. Collectively, our results suggest that brain region-specific metabolic disorders may be responsible for diabetes-induced cognitive dysfunction. Keywords Diabetes . Brain region . Cognitive decline . Metabolomics . Neurotransmitter
Introduction Type 1 diabetes (T1D) as a chronic autoimmune disease is caused by the destruction of pancreatic beta-cells and characterized by insulin deficiency and hyperglycemia (Azhir et al. 2018; MacNaught and Holt 2015; Mikk et al. 2017). The prevalence of T1D is gradually increasing in the world (Murfitt et al. 2018) and typically occurs in children and juveniles (Hletala et al. 2010). Of note, T1D can cause a series of complications including Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11011-020-00598-z) contains supplementary material, which is available to authorized users. Tingting Zhang and Hong Zheng contributed equally to this work. * Hongchang Gao [email protected] * Yunjun Yang [email protected] 1
Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China
2
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
cognitive impairment, which severely affect the quality of human life (Stern et al. 2002). Several potential mechanisms underlying diabetes-induced cognitive decline have been reported. For example, hyperglycemia can give rise to cognitive dysfunction by increased formation of reactive oxygen species and advanced glycation end-products, excessive release of cytokines and inflammation (Yagihashi et al. 2011). T1D-driven cognitive decline may be attributed to the reductions of white matter volume (Wessels et al. 2007) and functional connectivity (Duinkerken et al. 2012). Moreover, brain metabolic abnormality could also be implicated in diabetes-induced cognitive decline (Duarte 2015
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