The objective of this proposal is to use nuclear magnetic resonance (NMR) spectroscopy to gain a better understanding of CNS and PNS myelin structure. The long-term objective is to investigate the dynamic structure of normal human myelin, as a function of development, to study differences between normal myelin and diseased myelins (e.g. from Multiple Sclerosis (MS) and Alzheimers' disease), and to study phylogentic relationships. To achieve these goals, we will use 1H and 13C magic-angel sample spinning (MASS) NMR spectroscopy, at a variety of magnetic field strengths, to obtain quantitative information on chemical composition, and via relaxation analyses, on dynamic structure. We will initially study the MASS NMR behavior of a series of phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin) and glycolipids (cerebrosides), together with studies of simple (smectic, hexagonal, cubic, cholesteric) liquid crystals, then will investigate lipid interactions with the two major myelin membrane proteins, the basic protein (MBP) and the proteolipid proteins (PLP,P0). The next phase will involve similar NMR studies of intact myelin, where we can now resolve and assign up to 25 types of 13C resonance (e.g. from the choline headgroup, from the cerebroside sugar headgroup, from PE, from cholesterol, and from the alkyl chain region). In this way, we will build up a picture about the various interactions between the lipid, protein and sterol constituents of normal myelin, which can be compared with abnormal myelin structure, with myelin development, with myelin structure from different brain regions, and with myelin structure in invertebrates, and in aquatic, amphibious and terrestrial craniates. Supplementary DSC, XRD and FTIR spectroscopic studies will be carried out with Professor M. A. Moscarello (Toronto) and Professor D. Chapman, F.R.S. (London). NMR experiments will all be carried out in Urbana using primarily 360 and 500 MHz spectrometers. The health- relatedness of the research is that we will obtain, using the new 1H and 13C MASS NMR techniques, a large new body of information on the structure of both CNS and PNS myelins in normal and abnormal systems.
