Localization of Endogenous Metabolites in Diabetic Mouse Brain Tissue via MALDI Imaging Mass Spectrometry

摘要

Molecularly specific imaging of small endogenous metabolites is complicated by the presence of many nominally and exactly isobaric species, all having a high degree of structural homology. Accurate mass or single MS/MS transitions are often not sufficient to unambiguously identify the species of interest. We have utilized several MS~3 methods in addition to accurate mass to investigate metabolomic changes in the brains of diabetic mice. We have found an unexpected increase in ATP in the amygdala region of STZ brains compared to controls. Similarly, we found a species at m/z 376.9447, consistent with fructose bisphosphate via high mass accuracy (<0.1 ppm) that seemed to be overexpressed in the hippocampus region of STZ brains. Since fructose-1,6-bisphosphate lies within the glycolysis metabolic pathway, it is reasonable that its expression is altered in tissues exposed to high amounts of glucose via diabetes. We are in the process of examining upstream (i.e., fructose-6-phosphate) and downstream (i.e., glyceraldehyde-3-phosphate and dihydroxyacetone phosphate) metabolites to determine if the increase is due to an increase in synthesis or a decrease in breakdown.