Analysis of phospholipids in neuronal tissue using electrospray ionization-mass spectrometry
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Phospholipids are an important constituent of all cell membranes, and are thought to play key roles in several physiological processes. This research focuses on the use of electrospray ionization-mass spectrometry (ESI-MS) in studying alterations in the phospholipid profiles of neuronal cells in response to different kinds of stress. First, alterations in phospholipid and fatty acid lipid profiles in primary neocortical cells during oxidant-induced cell injury were studied. Oxidant-induced alterations in phospholipid composition can lead to decreases in membrane integrity, cell injury and even death. Neurons are especially vulnerable to lipid peroxidation. Treatment with the oxidants hydrogen peroxide (H2O2) and tert-butylhydroperoxide (TBHP) was found to increase the abundance of phospholipids containing polyunsaturated fatty acids, but had minimal affect on those containing mono- or di-unsaturated fatty acids. In addition, Group IV and VI Phospholipase A2 (PLA2) were found to have differential roles in oxidant-induced neural cell injury based on the use of the group specific inhibitors, methyl arachidonyl flourophosphonate (MAFP) and bromoenol lactone (BEL) respectively. Secondly, the effects of cocaine withdrawal on the expression of glycerophospholipids in rat brain were studied. For the first time, differences in the expression of phospholipids between different areas of the rat brain were determined by ESI-MS. Withdrawal from cocaine appeared to effect expression of specific phospholipids in a site specific manner, with most of the changes taking place in the hippocampus, the region generally associated with long term memory and spatial navigation. This may explain the long term neuroadaptation associated with drug use.