The Role of Metabolomics in Brain Metabolism Research

Abstract

This special edition of the Journal of Neuroimmune Pharmacology focuses on the leading edge of metabolomics in brain metabolism research. The topics covered include a metabolomic field overview and the challenges in neuroscience metabolomics. The workflow and utility of different analytical platforms to profile complex biological matrices that include biofluids, brain tissue and cells, are shown in several case studies. These studies demonstrate how global and targeted metabolite profiling can be applied to distinguish disease stages and to understand the effects of drug action on the central nervous system (CNS). Finally, we discuss the importance of metabolomics to advance the understanding of brain function that includes ligand-receptor interactions and new insights into the mechanisms of CNS disorders.

Fig. 1

Central dogma of molecular biology and systems biology. Metabolites are biologically relevant endpoints that encompass the downstream products of cellular activity. They serve as a direct read out of the biochemical activity closely associated with phenotype of the biological system

Fig. 2

Accelerated global profiling by simultaneous quantification and identification of metabolites, followed by pathway mapping. The advances in mass spectrometers enable the sequential collection of high quality MS (for comparative quantitative analysis of different groups of samples) and MS/MS data (for MS/MS matching to facilitate metabolite identification) in a single run. ATP was identified and mapped onto purine metabolism pathway among other dysregulated metabolites (red color tone – level of significance)

Fig. 3

Nanostructure Imaging Mass Spectrometry (NIMS) of mouse brain. Extracted brain map shows the white-gray matter distribution of one brain sulfatide. Image was acquired from a 2 uM brain section that was mounted on etched silicon chip, coated with perfluorinated-amino initiator, prior to imaging using laser desorption ionization technique in negative ionization mode. Data were acquired at 50 uM-spatial resolution of a laser beam

Fig. 4

Metabolomic workflow. Global profiling summarizes the experimental design with respect to metabolism quenching and global LC/MS profiling of different sample groups. LC/MS data acquisition is followed by retention time correction for chromatogram alignment and visualization of dysregulated metabolite features. Metabolite features whose levels were significantly changed in disease vs. control samples are than filtered out and identified by MS/MS matching. The identified metabolites are quantified by targeted MRM analysis using standard compounds