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Project

The absolute quantification of endogenous levels of neuromedin U and neuromedin S in vivo using nanoLC–ESI-MS/MS (FWOTM672)

Neuropeptides seem to play an important role when the central nervous system is challenged. In order to obtain better insights into the central peptidergic effects, it is essential to monitor their concentration in the brain. Quantification of neuropeptides in dialysates is challenging due to their low extracellular concentrations (low pM range), their low microdialysis efficiencies, the need for acceptable temporal resolution, the small sample volumes, the complexity of the matrix and the tendency of peptides to stick to glass and polymeric materials. The quantification of neuropeptides in dialysates therefore necessitates the use of very sensitive nanoLC-MS/MS methods. A number of LC-MS/MS and microdialysis parameters need to be optimized to achieve maximal sensitivity. In this project, we focus on the development of nanoLC-MS/MS methods for the quantification of 2 larger peptides (20-40 amino acids) in brain microdialysates. Both peptides belong to the neuromedin family and are involved in the regulation of the hypothalamo-pituitary-adrenal axis, which in turn is involved in the neurobiology of depression. Therefore, the optimized and validated methods will be used to investigate the in vivo neuromedin U and neuromedin S release in two rodent models for depression, in this way initiating new and immense challenges for the development of new drugs.
Date:1 Oct 2013 →  30 Sep 2017
Keywords:Aminoacids, Parkinsons Disease, Neuro-Transmitters, Neuropharmacology, clinical pharmacy, Stroke, Receptors, Rat Models, Neurochemistry, Pharmacokinetics, Microdialysis, Drug Research, neuroscience, Bioanalysis, Epilepsy, Neurosciences, seamless care, Monoamines, Liquid Chromatography, pharmaceutical care, Electrochemical Detection
Disciplines:Neuropsychology, Neurosciences, Chemical product design and formulation, Public health care, Drug discovery and development