Metabolomics of brain chemistry using LC-MS

• Grant number: 23/01712-6
• Support Opportunities: Scholarships abroad - Research
• Start date: August 01, 2023
• End date: June 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Carla Beatriz Grespan Bottoli
• Grantee: Carla Beatriz Grespan Bottoli
• Host Investigator: Robert Kennedy
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated research grant: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis, AP.TEM

Abstract

Neurons in the brain communicate via secretion of neurotransmitters and neuromodulators. Measuring these neurochemical signals can be valuable for understanding behavior, neurological diseases and drug effects on the brain. Although valuable neurochemical measurements can be made in ex vivo preparations, ultimately in vivo measurements are needed. Only in vivo measurements allow correlation of behavior with neurochemical concentrations. Further improvements in the analytical tools used for such measurements are required to overcome barriers such as relatively low number of compounds that can be identified and monitored, and low spatial resolution. New analytical tools also can develop the concept of determining state-specific brain chemistry and the coupling of sampling with LC-MS opens the possibility of discovery-based monitoring. In this project, we propose to enable routine monitoring of a substantially larger fraction of the brain metabolome and build a database of identifiable compounds in dialysate using compound identification strategies Kennedy´s group recently developed. We will develop miniaturized, ultra-high resolution chromatography columns for this application. The small column size will enable better sensitivity for the small samples collected. We also will evaluate different labeling reagents to label small molecules neurotransmitters and their metabolites, and then search for the label to do undirected metabolomics. Kennedy´s group is well-positioned to push this approach forward given his experience with in vivo sampling, miniaturized LC-MS, and connection to the Michigan Regional Center for Metabolomics Research Core (MRC2). (AU)