Search Results (2)

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and C9orf72 positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI. Full article

Mass spectrometry imaging is a powerful tool to analyze a large number of metabolites with their spatial coordinates collected throughout the sample. However, the significant differences in ionization efficiency pose a big challenge to metabolomic mass spectrometry imaging. To solve the challenge and obtain a complete data profile, researchers typically perform experiments in both positive and negative ionization modes, which is time-consuming. In this work, we evaluated the use of the dicationic reagent, 1,5-pentanediyl-bis(1-butylpyrrolidinium) difluoride (abbreviated to [C₅(bpyr)₂]F₂) to detect a broad range of metabolites in the positive ionization mode by infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI). [C₅(bpyr)₂]F₂ at 10 µM was doped in 50% MeOH/H₂O (v/v) electrospray solvent to form +1 charged adducted ions with anionic species (−1 charged) through post-electrospray ionization. This method was demonstrated with sectioned rat liver and hen ovary. A total of 73 deprotonated metabolites from rat liver tissue sections were successfully adducted with [C₅(bpyr)₂]²⁺ and putatively identified in the adducted positive ionization polarity, along with 164 positively charged metabolite ions commonly seen in positive ionization mode, which resulted in 44% increased molecular coverage. In addition, we were able to generate images of hen ovary sections showing their morphological features. Following-up tandem mass spectrometry (MS/MS) indicated that this dicationic reagent [C₅(bpyr)₂]²⁺ could form ionic bonds with the headgroup of glycerophospholipid ions. The addition of the dicationic reagent [C₅(bpyr)₂]²⁺ in the electrospray solvent provides a rapid and effective way to enhance the detection of metabolites in positive ionization mode. Full article