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Microglia and glutathione: Immune self-defence of the brain?
Vicky Fry 2007
Glutathione is the major intrinsic antioxidant in the mammalian central nervous system (CNS). Due to the high metabolic activity of the CNS large amounts of reactive oxygen species (ROS) are generated. Increases in ROS levels have been implicated in the pathogenesis of a number of neuroinflammatory and neurodegenerative diseases such as Alzheimer’s disease, therefore the elimination of these ROS is crucially important for a healthy CNS. It is known that astrocytes contain high levels of glutathione compared to neurones, and that they are able to release this to provide glutathione precursors to be taken up and converted into glutathione by neurones. Less is known about the glutathione system of microglia. These cells act as the immune surveillance cells of the CNS. However, chronic activation of microglia may lead to neuronal damage and neuroinflammation.
Here two methods are used to study reduced glutathione (GSH) levels in microglial cell lines and primary microglia; reverse-phase high performance liquid chromatography (HPLC) and imaging using the fluorescent GSH adduct monochlorobimane (MCB). HPLC data suggest that activation of microglia decreases intracellular GSH whilst MCB imaging experiments suggest the opposite. Limited amounts of published data are available which support both possibilities (Chatterjee et al 2000, Moss and Bates 2001, Persson et al 2006). Activation of microglia could affect the level and/or activity of the enzyme glutathione-S-transferase (GST) which conjugates MCB to GSH, thus affecting levels of the GSH-MCB adduct independent of intracellular GSH concentration. These results therefore highlight a drawback of this method and indicate the need for validation by determination of GST activity. An increase in microglial GSH concentration following activation could reflect a microglial self-preservation mechanism. A decrease may be a sign that the cells are unable to cope with the increased levels of ROS and may lead ultimately to microglial death. (Word count 297)