Home LiteratureArticle Details
PMID: 9444566 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease.

Journal of neural transmission (Vienna, Austria : 1996) ·Vol. 104 ·No. 6-7 ·1997-00-00 ·Pages 661-77

Pearce RK, Owen A, Daniel S, Jenner P, Marsden CD

Abstract

Depletion of reduced glutathione occurs in the substantia nigra in Parkinson's disease and in incidental Lewy body disease (presymptomatic Parkinson's disease) which may implicate oxidative stress in the neurodegenerative process. In this study mercury orange fluorescent staining and immunostaining with an antibody to reduced glutathione have been used to determine the distribution of reduced glutathione in the substantia nigra in Parkinson's disease compared with normal individuals. Mercury orange staining showed moderate background levels of fluorescence in the neuropil in both control and Parkinson's disease substantia nigra and localised reduced glutathione to the somata of melanized nigral neurons and glial elements of the neuropil. Neuronal nuclei revealed a relative lack of fluorescence after mercury orange staining. There was a significant depletion of reduced glutathione in surviving neurons in Parkinson's disease compared to nerve cell populations in control tissue. Mercury orange fluorescence indicated a high concentration of reduced glutathione in a subpopulation of non-neuronal cells, most likely astrocytes or microglia. Immunohistochemical examination of nigral tissue from the same Parkinson's disease and control patients with an antibody to glutathione showed staining in neuronal perikarya and axonodendritic processes of melanized nigral neurons which was generally most intense in control neurons. Moderately intense staining of the background neuropil, most prominent in control nigras, and staining of capillary walls was also detected. Intense staining was seen in cells with the morphological features of glial cells in both control and PD nigra. These data show a significant presence of reduced glutathione in the cell bodies and axons of nigral neurons. They are in agreement with biochemical studies showing depletion of reduced glutathione in substantia nigra in Parkinson's disease, and indicate a significant loss of neuronal reduced glutathione in surviving nigral neurons in Parkinson's disease.

MeSH Terms
Aged Aged, 80 and over Case-Control Studies Coloring Agents Female Glutathione/metabolism Humans Immunohistochemistry Male Microscopy, Fluorescence Parkinson Disease/metabolism Phenylmercury Compounds Substantia Nigra/metabolism
Chemicals
Coloring Agents Phenylmercury Compounds Glutathione mercury orange
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pearce R K
Neurodegenerative Diseases Research Centre, King's College, London, United Kingdom.
Owen A
Daniel S
Jenner P
Marsden C D
References (42)
42 references, click to expand
  1. The mitochondrial electron transfer alteration as a factor involved in the brain aging.
    Neurobiol Aging. 1992 May-Jun;13(3):361-8 PMID: 1320745
  2. Concentric hyalin intraneuronal inclusions of Lewy type in the brains of elderly persons (50 incidental cases): relationship to parkinsonism.
    J Am Geriatr Soc. 1969 Jun;17(6):557-75 PMID: 4182529
  3. The presence of glutathione in primary neuronal and astroglial cultures from rat cerebral cortex and brain stem.
    J Neural Transm Gen Sect. 1991;86(1):43-9 PMID: 1751028
  4. Rate of cell death in parkinsonism indicates active neuropathological process.
    Ann Neurol. 1988 Oct;24(4):574-6 PMID: 3239957
  5. Microglia in degenerative neurological disease.
    Glia. 1993 Jan;7(1):84-92 PMID: 8423066
  6. Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease.
    J Neurochem. 1990 Dec;55(6):2142-5 PMID: 2121905
  7. Glutathione peroxidase, glial cells and Parkinson's disease.
    Neuroscience. 1993 Jan;52(1):1-6 PMID: 8433802
  8. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia.
    Ann Neurol. 1994 Sep;36(3):348-55 PMID: 8080242
  9. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
    J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745-52 PMID: 2841426
  10. Glutathione levels in olfactory and non-olfactory neural structures of rats.
    Brain Res. 1991 Mar 15;543(2):341-6 PMID: 1711912
  11. Histochemical evaluation of glutathione in brain.
    Brain Res. 1987 Apr 21;409(2):275-84 PMID: 3580876
  12. New insights into the cause of Parkinson's disease.
    Neurology. 1992 Dec;42(12):2241-50 PMID: 1461374
  13. Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons.
    Brain Res. 1989 Jul 31;493(2):398-401 PMID: 2765907
  14. Antibodies to reduced glutathione.
    Brain Res. 1994 Oct 3;659(1-2):237-42 PMID: 7820668
  15. Mitochondrial changes associated with glutathione deficiency.
    Biochim Biophys Acta. 1995 May 24;1271(1):35-42 PMID: 7599223
  16. Peroxidative block of glucose utilization and survival in CNS neuronal cultures.
    Neurochem Res. 1988 Jul;13(7):611-6 PMID: 2901050
  17. Increased excitotoxic vulnerability of cortical cultures with reduced levels of glutathione.
    Eur J Pharmacol. 1991 Jan 3;192(1):199-200 PMID: 1674918
  18. Parkinson's disease: a disorder due to nigral glutathione deficiency?
    Neurosci Lett. 1982 Dec 13;33(3):305-10 PMID: 7162692
  19. Glutathione-related enzymes in brain in Parkinson's disease.
    Ann Neurol. 1994 Sep;36(3):356-61 PMID: 8080243
  20. Screening of thiol compounds: depolarization-induced release of glutathione and cysteine from rat brain slices.
    J Neurochem. 1992 Jul;59(1):181-9 PMID: 1351924
  21. Cellular and regional distribution of reduced glutathione in the nervous system of the rat: histochemical localization by mercury orange and o-phthaldialdehyde-induced histofluorescence.
    Toxicol Appl Pharmacol. 1991 Feb;107(2):215-27 PMID: 1994508
  22. Glutathione in Parkinson's disease: a link between oxidative stress and mitochondrial damage?
    Ann Neurol. 1992;32 Suppl:S111-5 PMID: 1510368
  23. Glutathione deficiency leads to mitochondrial damage in brain.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1913-7 PMID: 2000395
  24. On the antioxidant effects of ascorbic acid and glutathione.
    Biochem Pharmacol. 1992 Nov 17;44(10):1905-15 PMID: 1449510
  25. Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients.
    Neurosci Lett. 1986 Jun 30;67(3):269-74 PMID: 3737015
  26. Antisera to glutathione: characterization and immunocytochemical application to the rat cerebellum.
    Eur J Neurosci. 1994 May 1;6(5):793-804 PMID: 8075821
  27. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.
    J Neurochem. 1989 Feb;52(2):515-20 PMID: 2911028
  28. Maintenance of neuronal glutathione by glial cells.
    J Neurochem. 1993 Nov;61(5):1672-6 PMID: 8228986
  29. L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress.
    J Neurochem. 1996 Feb;66(2):501-10 PMID: 8592119
  30. Ageing and Parkinson's disease: substantia nigra regional selectivity.
    Brain. 1991 Oct;114 ( Pt 5):2283-301 PMID: 1933245
  31. Oxygen toxicity protecting enzymes in Parkinson's disease. Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus.
    J Neurol Sci. 1988 Sep;86(2-3):321-31 PMID: 3221244
  32. Histochemical localization of glutathione in tissues.
    J Histochem Cytochem. 1975 Oct;23(10):774-9 PMID: 53246
  33. Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells.
    Brain Res. 1995 May 22;680(1-2):16-22 PMID: 7663973
  34. A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra.
    J Neurochem. 1989 Sep;53(3):692-7 PMID: 2760616
  35. Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease.
    Neurosci Lett. 1990 Mar 2;110(1-2):216-20 PMID: 2325885
  36. Reduction of brain glutathione by L-buthionine sulfoximine potentiates the dopamine-depleting action of 6-hydroxydopamine in rat striatum.
    J Neurochem. 1989 Mar;52(3):978-80 PMID: 2493072
  37. The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E.
    Eur J Biochem. 1988 Jun 1;174(2):353-7 PMID: 3383850
  38. Idiopathic Parkinson's disease and the Lewy body disorders.
    Neuropathol Appl Neurobiol. 1986 May-Jun;12(3):223-34 PMID: 3016582
  39. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia.
    Brain. 1991 Aug;114 ( Pt 4):1953-75 PMID: 1832073
  40. Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain.
    J Neurochem. 1994 Jan;62(1):45-53 PMID: 7903354
  41. Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease.
    Ann Neurol. 1994 Jan;35(1):38-44 PMID: 8285590
  42. Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson's Disease Research Group.
    Ann Neurol. 1992;32 Suppl:S82-7 PMID: 1510385
Article Info
Journal
Journal of neural transmission (Vienna, Austria : 1996)
Abbr.
J Neural Transm (Vienna)
ISSN
0300-9564
DOI
10.1007/BF01291884
Published
1997-00-00
Pages
661-77
Language
English
Region
Austria
NLM ID
9702341
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01291884 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2