Peroxides are generated continuously in cells that consume oxygen. Among the different peroxides, hydrogen peroxide is the molecule that is formed in highest quantities. In addition, organic hydroperoxides are synthesized as products of cellular metabolism. Generation and disposal of peroxides is a very important process in the human brain, because cells of this organ consume 20% of the oxygen used by the body. To prevent cellular accumulation of peroxides and damage generated by peroxide-derived radicals, brain cells contain efficient antioxidative defense mechanisms that dispose of peroxides and protect against oxidative damage. Cultured brain cells have been used frequently to investigate peroxide metabolism of neural cells. Efficient disposal of exogenous hydrogen peroxide was found for cultured astrocytes, oligodendrocytes, microglial cells, and neurons. Comparison of specific peroxide clearance rates revealed that cultured oligodendrocytes dispose of the peroxide quicker than the other neural cell cultures. Both catalase and the glutathione system contribute to the clearance of hydrogen peroxide by brain cells. For efficient glutathione-dependent reduction of peroxides, neural cells contain glutathione in high concentration and have substantial activity of glutathione peroxidase, glutathione reductase, and enzymes that supply the NADPH required for the glutathione reductase reaction. This article gives an overview on the mechanisms involved in peroxide detoxification in brain cells and on the capacity of the different types of neural cells to dispose of peroxides.
A population of neurons in the caudal medulla generates the rhythmic activity underlying breathing movements. Although this neuronal network has attracted great attention for studying neuronal aspects of synaptic transmission, functions of glial cells supporting this neuronal activity remain unclear. To investigate the role of astrocytes in the respiratory network, we applied electrophysiological and immunohistochemical techniques to characterize astrocytes in regions involved in the generation and transmission of rhythmic activity. In the ventral respiratory group and the hypoglossal nucleus (XII) of acutely isolated brainstem slices, we analyzed fluorescently labeled astrocytes obtained from TgN(GFAP-EGFP) transgenic mice with the whole-cell voltage-clamp technique. Three subpopulations of astrocytes could be discerned by their distinct membrane current profiles. A first group of astrocytes was characterized by nonrectifying, symmetrical and voltage-independent potassium currents and a robust glutamate transporter response to D-aspartate. A second group of astrocytes showed additional A-type potassium currents, whereas a third group, identified by immunolabeling for the glial progenitor marker NG2, expressed outwardly rectifying potassium currents, smaller potassium inward currents, and only minimal D-aspartateinduced transporter currents. Astrocytes of all groups showed kainate-induced inward currents.We conclude that most of the astrocytes serve as a buffer system of excess extracellular glutamate and potassium; however, a distinct cell population (NG2-positive, A-type potassium currents) may play an important role for network plasticity.
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