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Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson’s disease and dementia with Lewy bodies

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Abstract

Glutathione peroxidase (GPx-1) is regarded as one of the mammalian cell’s main antioxidant enzymes inactivating hydrogen peroxide and protecting against oxidative stress. Using control, Parkinson’s disease (PD), and dementia with Lewy bodies tissue (DLB) we have shown that GPx-1 is a 21-kD protein under reducing conditions in all tissues examined but is not in high abundance in human brain. Using immunohistochemistry we have mapped the cellular distribution of GPx-1 and have shown it to be in highest levels in microglia and with lower levels in neurons. Only a trace amount was detectable in astrocytes using immunofluorescence and GPx-1 was not detectable in oligodendrocytes. GPx-1 positive microglia were hypertrophied and more abundant in PD and DLB tissues and were seen to be making multiple contacts with neurons. In some cases neurons containing Lewy bodies were surrounded by microglia. Unstructured Lewy bodies were enveloped with a layer of GPx-1 that was partially colocalized with α-synuclein whereas concentric Lewy bodies had discrete deposits of GPx-1 around the periphery which appeared to be involved in the degradation of the Lewy bodies. These results suggest that abnormal α-synuclein as found in Lewy bodies produce hydrogen peroxide and these neurons are capable of directing antioxidant enzymes to regions of oxidative stress. These results also suggest that GPx-1 positive microglia are involved in neuroprotection in PD and DLB and that GPx-1 is an important antioxidant enzyme in neuronal defences.

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Acknowledgments

We gratefully acknowledge the excellent assistance of the Flinders University Flinders University Microscopy and Image Analysis Facility and the South Australian Brain Bank. We also acknowledge the excellent technical assistance of Ms. Karen Humphreys and Ms. Christiane Simon. The useful discussions with Mr. James Manavis, Dr. Weiping Gai, and Professor James Temlett are gratefully acknowledged. This work was supported by the Flinders Medical Centre Foundation and a Flinders University Faculty Grant.

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Authors and Affiliations

  1. Department of Human Physiology, School of Medicine, Flinders University of South Australia, Adelaide, SA, 5042, Australia

    John H. T. Power

  2. Institute of Medical and Veterinary Science, Adelaide, SA, Australia

    Peter C. Blumbergs

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Correspondence to John H. T. Power.

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Power, J.H.T., Blumbergs, P.C. Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol 117, 63–73 (2009). https://doi.org/10.1007/s00401-008-0438-3

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  • DOI: https://doi.org/10.1007/s00401-008-0438-3

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