NextGen Brain Microdialysis: Applying Modern Metabolomics Technology to the Analysis of Extracellular Fluid in the Central Nervous System.
Microdialysis is a powerful method for in vivo neurochemical analyses. It allows fluid sampling in a dynamic manner in specific brain regions over an extended period of time. A particular focus has been the neurochemical analysis of extracellular fluids to explore central nervous system functions. Brain microdialysis recovers neurotransmitters, low-molecular-weight neuromodulators and neuropeptides of special interest when studying behavior and drug effects. Other small molecules, such as central metabolites, are typically not assessed despite their potential to yield important information related to brain metabolism and activity in selected brain regions. We have implemented a liquid chromatography online mass spectrometry metabolomics platform for an expanded analysis of mouse brain microdialysates. The method is sensitive and delivers information for a far greater number of analytes than commonly used electrochemical and fluorescent detection or biochemical assays. The metabolomics platform was applied to the analysis of microdialysates in a foot shock-induced mouse model of posttraumatic stress disorder (PTSD). The rich metabolite data information was then used to delineate affected prefrontal molecular pathways that reflect individual susceptibility for developing PTSD-like symptoms. We demonstrate that hypothesis-free metabolomics can be adapted to the analysis of microdialysates for the discovery of small molecules with functional significance.
Departments of Translational Research in Psychiatry, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilian University, Munich, Germany.
Chi-Ya
CY
Kao
Departments of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Elmira
E
Anderzhanova
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Mass., USA; Department of Medicine, Harvard Medical School, Boston, Mass., USA.
John M
JM
Asara
Departments of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Carsten T
CT
Wotjak
Departments of Translational Research in Psychiatry, Munich, Germany.
Christoph W
CW
Turck
Biomarker; Metabolite profiling; Microdialysis; Molecular pathways; Posttraumatic stress disorder; Stress susceptibility and resilience