Objective: Metabolomics is applied to the study of metabolic as well as neurodegenerative diseases. We propose to utilize this technique to detect metabolic changes from Deep Brain Stimulation (DBS) for PD.

Background: Metabolomics is dedicated to investigating small molecule metabolites in biofluids and tissues and can represent direct assessment of disease phenotype. Metabolomics is emerging as a powerful tool for the characterization and identification of biomarkers and for fingerprinting the metabolic status of physiological processes in tissue, blood and other samples.

Methods: Snap frozen tissue from a patient who had undergone DBS for PD was utilized. Pieces of tissue were removed immediately surrounding the DBS electrode along a linear plane and also from the untreated, contralateral hemisphere. Samples were subject to LC-HRMS global metabolomic profiling. Metabolomic analysis was performed on a Thermo Q-Exactive high resolution mass spectrometer in both the positive and negative ion mode. Peak alignment and mass spectral data reduction was performed with MZmine. Metaboanalyst was used for statistical analysis. Using multivariate techniques, a number of unique small molecule metabolites were identified.

Results: Tissue samples were de-identified to remove bias during analyses. Unsupervised multivariate statistical analysis identified 3 distinct regions of the brain significantly different from others. These were in the immediate vicinity of the active DBS electrode, and differed significantly from other, non-DBS (control) regions. Analysis of individual metabolites revealed several known and unknown chemical signatures uniquely expressed in the DBS region. Metabolites expressed in significantly higher amounts in the DBS region included those that may provide potential for reduction in free radical induced damage to the brain and included propionyl carnitine and ergothioneine. The former is thought to be neuroprotective and the latter is thought to be able to scavenge reactive oxygen species.

Conclusions: We have shown feasibility of sampling tissue from small regions of post-mortem human brain for metabolomic studies. This approach enabled us to identify brain regions distinctly different from each other based on metabolomic signatures. These unique signatures may aid in uncovering the molecular basis of DBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-unique-metabolite-signatures-in-post-mortem-dbs-human-tissue-using-lc-hrms/