caa a22 4500 445376694 CHVBK 20180317143004.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00702-010-0489-1 doi (NATIONALLICENCE)springer-10.1007/s00702-010-0489-1 Iron mediates neuritic tree collapse in mesencephalic neurons treated with 1-methyl-4-phenylpyridinium (MPP+) [Elektronische Daten] [Francisco Gómez, Pabla Aguirre, Christian Gonzalez-Billault, Marco Núñez] Studies in post-mortem tissues of patients with Parkinson's disease (PD) and in mice treated with 6-hydroxydopamine have shown a decrease in the length of axon and dendrites of striatal neurons. However, the etiology of the morphological changes and their relationship to inhibition of mitochondrial complex I and the cellular levels of iron and glutathione (GSH) have not been described. In this study, we characterized the effect of MPP+, an inhibitor of mitochondria complex I, on the integrity of the neuritic tree of midbrain dopaminergic neurons, and determined the influence of iron and cellular levels of GSH on this degeneration. Sub-maximal concentrations of MPP+ induced a drastic dose-dependent reduction of neurites, without modification of the soma or apparent cell death. Concurrent treatment with MPP+ and non-toxic concentrations of iron accelerated the process of degeneration, whereas neurons grown on a medium low in iron showed enhanced resistance to MPP+ treatment. MPP+-induced neurite shortening depended on the redox state of neurons. Pre-treatment with the general antioxidant N-acetyl cysteine protected neurons from degeneration. Treatment with sub-maximal concentrations of the inhibitor of GSH synthesis buthionine sulfoximine (BSO), in conjunction with iron and MPP+, produced massive cell death, whereas treatment with BSO plus MPP+ under low iron conditions did not damage neurons. These results suggest that under conditions of inhibition of mitochondrial complex I caused by MPP+, the accumulation of iron and the concurrent decrease in GSH results in the loss of the dendritic tree prior to cell death, of dopaminergic neurons in PD. Springer-Verlag, 2010 Iron nationallicence Parkinson nationallicence Glutathione nationallicence Complex I nationallicence Antioxidants nationallicence Gómez Francisco Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut Aguirre Pabla Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut Gonzalez-Billault Christian Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut Núñez Marco Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 421-431 0300-9564 118:3<421 2011 118 702 https://doi.org/10.1007/s00702-010-0489-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0489-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gómez Francisco Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut NATIONALLICENCE 700 1- Aguirre Pabla Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut NATIONALLICENCE 700 1- Gonzalez-Billault Christian Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut NATIONALLICENCE 700 1- Núñez Marco Department of Biology, Faculty of Sciences, Cell Dynamics and Biotechnology Institute, Universidad de Chile, Santiago, Chile aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/3(2011-03-01), 421-431 0300-9564 118:3<421 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer