Spatially Resolved Metabolomics Based on Air-Flow-Assisted Desorption Electrospray Ionization–Mass Spectrometry Imaging Reveals Region-Specific Metabolic Alterations in Diabetic Encephalopathy

Spatially resolved metabolic profiling of brain is vital for elucidating tissue-specific molecular histology and pathology underlying diabetic encephalopathy (DE). In this study, a spatially resolved metabolomic method based on air-flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was developed for investigating the region-specific metabolic disturbances in the brain of DE model rats induced by a high-fat diet in combination with streptozotocin administration. A total of 19 discriminating metabolites associated with glycolysis and the pentose phosphate pathway (PPP); the glutamate/gamma aminobutyric acid-glutamine cycle and tricarboxylic acid cycle; nucleotide metabolism; lipid metabolism; carnitine homeostasis; and taurine, ascorbic acid, histidine, and choline metabolism were identified and located in the brains of the diabetic rats simultaneously for the first time. The results indicated that increased glycolytic and PPP activity; dysfunction of mitochondrial metabolism; dysregulation of adenosinergic, glutamatergic, dopaminergic, cholinergic, and histaminergic systems; disorder of osmotic regulation and antioxidant system; and disorder of lipid metabolism occur in a region-specific fashion in the brains of DE rats. Thus, this study provides valuable information regarding the molecular pathological signature of DE. These findings also underline the high potential of AFADESI-MSI for applications in various central nervous system diseases.