Lipidoma regional da estrutura encefálica e modulações da expressão lipídica radioinduzidas no encéfalo em modelo animal wistar

Abstract

The present work addresses the analysis of scientific findings in the study of brain lipidoma, and radioinduced modulations of brain lipids, using the DESI-MSI (Desorption Electrospray Ionization Mass Spectrometry Imaging) technique. Mass spectrometry (MS), through mild ionization at ambient atmospheric pressure, promotes the desorption of lipids allowing the qualitative and quantitative realization of numerous classes of lipids. The main objective was the lipidomic analysis of data produced in DESI-MSI in brain tissue under normal conditions and exposed to radiation, in an animal model. The methodology involved an animal model consisting of 40 healthy male isogenic Wistar rats that were divided into two groups: a control (n = 7), called GC and another submitted to total body irradiation (TBI), called GIR (n = 33) subdivided in 04 subgroups corresponding to time kinetics 24, 48, 96 h and 01 weeks. The animals (GIR group) underwent whole-body irradiation through exposure to a Co-60 source, submitted to the same conditions of time and dose (5 Gy). After euthanasia, considering the different kinetics of time to be analyzed, the organs were collected and stored in a freezer at -80ºC so that later the procedures to obtain the cuts in cryostat could be carried out. The slides were subjected to a methodology known as DESI-MSI that allows point-to-point 2D imaging. A full scan was performed in the range from 200 to 1000 Da, obtaining mass spectra in negative mode. The lipid data files produced by DESI-MSI were analyzed using BioMap and XCalibur software in the low and high molecular weight spectrum, exploring brain regionalization of lipid expression and radioinduced lipidomic modulation. An identification of the main lipids expressed under physiological conditions and exposed to radiation was carried out. The main findings came from the lipidomic analysis. The analyzes allowed the identification mainly of glycerophospholipids, due to the diversity of cellular functions they exert and the possibility of being biomarkers of possible radio-induced alterations. Most of the ions observed in the mass spectra correspond to deprotonated free fatty acids, phosphatidylserines (PS), phosphatidylinositols (PI) and sulfatides (ST). Several ions undergo changes in intensity and region of origin demonstrating the effect of radiation on brain tissue metabolome. The ion m/z 868.529, for example, had a spatial distribution present mainly in the cerebellar lobes (culmina, central lobe, slope, pyramid and uvula) and after irradiation there was a progressive decrease in the intensity of this lipid in all regions in all time kinetics. The findings of analytical data and imaging by DESI-MSI allow us to state that radiation induces metabolomic alterations in the brain lipid profile, in specific regions of the brain. Countless research possibilities in the field of metabolomics were opened, such as radiolipidomics of the brain. Toxicity biomarkers may be used in radiotherapy for better therapeutic control of toxicities.