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Profiling and Imaging of Peptides and Proteins in Brain Tissue using Mass Spectrometry as a Discovery Tool in Experimental Parkinson’s Disease

Per E. Andrén

Department of Pharmaceutical Biosciences, Medical Mass Spectrometry, Uppsala University, Uppsala, Sweden

Imaging Mass Spectrometry (IMS) can be used to locate specific molecules such as peptides and small proteins directly from fresh frozen tissue sections. Using matrix-assisted laser desorption ionization (MALDI) MS a raster of mass spectra over a given area of a section can be created. Images of samples are produced in specific m/z values, or ranges of values. The resulting spectrum contains hundreds of peptide and protein signals. Individual m/z values can then be assembled from these mass spectra to produce selected m/z images. Sample preparation in MALDI imaging is a crucial aspect in studying peptides and proteins in tissue. Brain tissue sections from animal models of Parkinson’s disease (PD) were spotted with different MALDI matrices (DHB, CHCA, SA) and imaged to locate and map tissue specific peptides and proteins. Different spatial resolutions of matrix droplets were applied to individual tissue slices. Using a mouse PD model (MPTP) data analysis revealed new peptides and proteins differently expressed in the dopamine denervated tissue but not the corresponding normal tissue. For example, IMS showed that the protein PEP-19, a neuronal calmodulin-binding protein and a putative modulator of calcium regulated processes, was predominantly localized to the striatum of the brain tissue cross sections. After MPTP administration, PEP-19 levels were significantly reduced by 30%.  IMS is an effective discovery tool for the analysis of proteins and peptides in tissues and is useful for the comparison of molecular weight based protein patterns in unhealthy versus normal tissues.

Seminar October 18, 2007_Per E. Andrén and Sarah Fredriksson Back