Spatially-resolved metabolic profiling of living Drosophila in neurodegenerative conditions using (1)H magic angle spinning NMR

Drosophila flies are versatile animal models for the study of gene mutations in neuronal pathologies. Their small size allows performing in vivo Magic Angle Spinning (MAS) experiments to obtain high-resolution (1)H nuclear magnetic resonance (NMR) spectra. Here, we use spatially-resolved (1)H high-resolution MAS NMR to investigate in vivo metabolite contents in different segments of the fly body. A comparative study of metabolic changes was performed for three neurodegenerative disorders: two cell-specific neuronal and glial models of Huntington disease (HD) and a model of glutamate excitotoxicity. It is shown that these pathologies are characterized by specific and sometimes anatomically localized variations in metabolite concentrations. In two cases, the modifications of (1)H MAS NMR spectra localized in fly heads were significant enough to allow the creation of a predictive model.