%A Dong,Minjian %A Ren,Mengqian %A Li,Chen %A Zhang,Xi %A Yang,Changwei %A Zhao,Liangcai %A Gao,Hongchang %D 2019 %J Frontiers in Cellular Neuroscience %C %F %G English %K Lactate,diabetic encephalopathy (DE),nuclear magncic resonance,Metabolomics,hydroxycarboxylic acid receptor 1 %Q %R 10.3389/fncel.2018.00527 %W %L %M %P %7 %8 2019-January-14 %9 Original Research %# %! Time-dependently Metabolic changes in diabetic brains %* %< %T Analysis of Metabolic Alterations Related to Pathogenic Process of Diabetic Encephalopathy Rats %U https://www.frontiersin.org/articles/10.3389/fncel.2018.00527 %V 12 %0 JOURNAL ARTICLE %@ 1662-5102 %X Diabetic encephalopathy (DE) is a diabetic complication characterized by alterations in cognitive function and nervous system structure. The pathogenic transition from hyperglycemia to DE is a long-term process accompanied by multiple metabolic disorders. Exploring time-dependent metabolic changes in hippocampus will facilitate our understanding of the pathogenesis of DE. In the present study, we first performed behavioral and histopathological experiments to confirm the appearance of DE in rats with streptozotocin-induced diabetes. We then utilized nuclear magnetic resonance-based metabonomics to analyze metabolic disorders in the hippocampus at different stages of DE. After 1 week, we observed no cognitive or structural impairments in diabetic rats, although some metabolic changes were observed in local hippocampal extracts. At 5 weeks, while cognitive function was still normal, we then examined initial levels of neuronal apoptosis. The characteristic metabolic changes of this stage included elevated levels of energy metabolites (i.e., ATP, ADP, AMP, and creatine phosphate/creatine). At 9 weeks, significant cognitive decline and histopathological brain damage were observed, in conjunction with reduced levels of some amino acids. Thus, this stage was classified as the DE period. Our findings indicated that the pathogenesis of DE is associated with time-dependent alterations in metabolic features in hippocampal regions, such as glycolysis, osmoregulation, energy metabolism, choline metabolism, branched-chain amino acid metabolism, and the glutamate–glutamine cycle. Furthermore, we observed alterations in levels of lactate and its receptor in hippocampal cells, which may be involved in the pathogenesis of DE.