NDLI: Alteration of Interaction Between Astrocytes and Neurons in Different Stages of Diabetes: a Nuclear Magnetic Resonance Study Using [1-$^{13}$C]Glucose and [2-$^{13}$C]Acetate

Content Provider	Springer Nature Link
Author	Wang, Na Zhao, Liang Cai Zheng, Yong Quan Dong, Min Jian Su, Yongchao Chen, Wei Jian Hu, Zi Long Yang, Yun Jun Gao, Hong Chang
Copyright Year	2014
Abstract	Increasing evidence has shown that the brain is a site of diabetic end-organ damage. This study investigates cerebral metabolism and the interactions between astrocytes and neurons at different stages of diabetes to identify the potential pathogenesis of diabetic encephalopathy. [1-$^{13}$C]glucose or [2-$^{13}$C]acetate is infused into 1- and 15-week diabetic rats, the brain extracts of which are analyzed by using $^{1}$H and $^{13}$C magnetic resonance spectroscopy. The $^{13}$C-labeling pattern and enrichment of cerebral metabolites are also investigated. The increased $^{13}$C incorporation in the glutamine, glutamate, and γ-aminobutyric acid carbons from [2-$^{13}$C]acetate suggests that the astrocytic mitochondrial metabolism is enhanced in 1-week diabetic rats. By contrast, the decreased labeling from [1-$^{13}$C]glucose reflected that the neuronal mitochondrial metabolism is impaired. As diabetes developed to 15 weeks, glutamine and glutamate concentrations significantly decreased. The increased labeling of glutamine C4 but unchanged labeling of glutamate C4 from [2-$^{13}$C]acetate suggests decreased astrocyte supply to the neurons. In addition, the enhanced pyruvate recycling pathway manifested by the increased lactate C2 enrichment in 1-week diabetic rats is weakened in 15-week diabetic rats. Our study demonstrates the overall metabolism disturbances, changes in specific metabolic pathways, and interaction between astrocytes and neurons during the onset and development of diabetes. These results contribute to the mechanistic understanding of diabetes pathogenesis and evolution.
Starting Page	843
Ending Page	852
Page Count	10
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	51
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2014-07-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Diabetic encephalopathy Pathogenesis $^{13}$C magnetic resonance spectroscopy Pyruvate recycling Anaplerotic pathway Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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