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|Title:||Profiling and Imaging the Nervous System With Mass Spectrometry|
|Author(s):||Monroe, Eric Britain|
|Doctoral Committee Chair(s):||Sweedler, Jonathan V.|
|Department / Program:||Chemistry|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||The functioning of biological systems relies on the complex interaction of a wide range of compounds under chemical, spatial, and temporal constraints. Beyond these controls, a wide range of spatial, concentration, and molecular sizes are involved as well. As could be expected, studying the complex interactions between cells in the nervous system which, in humans, contains ∼1012 neurons is a daunting analytical task.
In this dissertation, several different forms of mass spectrometry are used to study the spatial distribution of compounds in the nervous system of tissues and single cells from several different model systems. To this end, mass spectrometric imaging (MSI) is utilized to create distribution maps for selected signals which correspond to the localization of a given compound within the sample at single cell and subcellular spatial resolutions with secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS). MSI allows for both the identity and distribution of known and uncharacterized compounds to be studied in a single experiment as no prior knowledge of the imaged compounds is required. Additionally, many images may be created from a single experiment owing to the multiplexed detection capabilities of mass spectrometry.
The work presented here covers a varied landscape of biological mass spectrometric imaging and profiling experiments. Single neurons have been imaged with SIMS to uncover the heterogeneous distribution of vitamin E in the neuronal membrane. Additionally, the three-dimensional MS imaging of single cells is presented with SIMS and spinal cord tissues are examined with both SIMS and MALDI MS to uncover the distribution of a wide range of compounds ranging from atomic ions to traditional neuropeptides. Beyond traditional MSI approaches, a novel methodology for the rapid preparation of approximately single cell-sized samples from tissue sections for MALDI MS analysis is presented. An additional aspect of this work does not involve MSI but rather the discovery of novel neuropeptides from the sea urchin, which utilized similar methods as those used for characterizing signals observed in imaging experiments.
The sum of this work demonstrates the utility of mass spectrometry for the spatially resolved analysis of neurological tissues and cells from a variety of animal model systems to address biological questions towards understanding the intricacies of cell-to-cell signaling in the nervous system.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.
|Date Available in IDEALS:||2014-12-17|