NADPH-diaphorase/nitric oxide synthase containing neurons in normal and Parkinson's disease putamen

  • R. Böckelmann
  • G. Wolf
  • G. Ransmayr
  • P. Riederer
Full Papers

Summary

Nitric oxide (NO) is thought to be involved in neurodegenerative processes. Concerning Parkinson's disease (PD) it remains to be elucidated, if NO contributes to pathological alterations in the striatum. The present study evaluates the post-mortem putamen of PD patients and control subjects for distribution patterns of NO-synthase containing neurons, using the NADPH-diaphorase technique. The ratio of positively stained neurons and the total number of cells (control: 1,120±69 per mm2, n=5; PD: 575±164mm2, n=5) shows striking differences between controls and PD patients. Our findings give reason to conclude that NADPH-diaphorase positive structures may have pathogenetic importance in degenerative processes in PD putamen.

Keywords

Parkinson's disease putamen NADPH-diaphorase nitric oxide synthase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beal MF, Kowall NW, Swartz KJ, Ferrante RJ (1990a) Homocysteic acid lesions in rat striatum spare somatostatin-neuropeptide Y (NADPH-diaphorase) neurons. Neurosci Lett 108: 36–42Google Scholar
  2. Beal MF (1992) Role of excitotoxicity in human neurological disease. Curr Opin Neurobiol 2: 657–662Google Scholar
  3. Bugiani O, Perdelli F, Salvarani S, Leonardi A, Moncardi GL (1980) Loss of striatal neurons in Parkinson's disease: a cytometeric study. Eur Neurol 19: 339–344Google Scholar
  4. Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991a) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88: 7797–7801Google Scholar
  5. Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH (1991b) Nitrix oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 88: 6368–6371Google Scholar
  6. Ferrante RJ, Kowall NW, Beal MF, Richardson Jr EP, Bird ED, Martin JB (1985) Selective sparing of a class of striatal neurons in Huntington's disease. Science 230: 561–563Google Scholar
  7. Ferrante RJ, Kowall NW, Beal MF, Martin JB, Bird ED, Richardson Jr EP (1987) Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease. J Neuropathol Exp Neurol 46: 12–27Google Scholar
  8. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84: 5976–5980Google Scholar
  9. Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88: 2811–2814Google Scholar
  10. Izumi Y, Benz AM, Clifford DB, zorumski CF (1992) Nitric oxide inhibitors attenuate N-methyl-D-aspartate exitotoxicity in rat hippocampal slices. Neurosci Lett 135: 227–230Google Scholar
  11. Knowles RG, Palacios M, Palmer RMJ, Moncada S (1990) Kinetic characteristics of nitrix oxide synthase from rat brain. Biochem J 269: 207–210Google Scholar
  12. Koh J-Y, Peters S, Choi DW (1986) Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity. Science 234: 73–76Google Scholar
  13. Koh J-Y, Choi DW (1988a) Cultured striatal neurons containing NADPH-diaphorase or acetylcholinesterase are selectively resistant to injury by NMDA receptor agonists. Brain Res 446: 374–378Google Scholar
  14. Koh J-Y, Choi DW (1988b) Vulnarability of cultured cortical neurons to demage by excitoxins: different susceptibility of neurons containing NADPH-diaphorase. J Neurosci 8: 2153–2163Google Scholar
  15. Kornhuber J, Riederer P (1993) N-methyl-D-aspartate (NMDA) antagonists in Parkinson's disease. J Neurol Neurosurg Psychiatry 56: 427Google Scholar
  16. Kowall NW, Ferrante RJ, Martin JB (1987) Patterns of cell loss in Huntington's disease. Trends Neurosci 10: 24–29Google Scholar
  17. Lei SZ, Pan Z-H, Aggarwal SK, Chen H-SV, Hartman J, Sucher NJ, Lipton SA (1992) Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex. Neuron 8: 1087–1099Google Scholar
  18. Manzoni O, Prezeau L, Marin P, Deshager S, Bockaert J, Fagni L (1992) Nitric oxide-induced blockade of NMDA receptors. Neuron 8: 653–662Google Scholar
  19. Moncada C, Lekieffre D, Arvin B, Meldrum B (1992) Effect of NO synthase inhibition on MNDA- and ischemia-induced hippocampal lesions. NeuroReport 3: 530–532Google Scholar
  20. Moncada S, Palmer RMJ (1992) L-Arginine: nitric oxide pathway. In: Zilla P, Fasol R, Callow A (eds) Applied cardiovascular biology 1990–91. Int Soc Appl Cardiovasc Biol, vol 2. Karger, Basel, pp 139–151Google Scholar
  21. Morton AJ, Nicholson LFB, Faull RLM (1993) Compartmental loss of NADPH diaphorase in the neuropil of the human striatum in Huntington's disease. Neuroscience 53: 159–168Google Scholar
  22. Olney JW (1991) Exitotoxicity and neuropsychiatric disorders. In: Ascher P, Choi DW, Christen Y (eds) Glutamate, cell death and memory. Springer, Berlin Heidelberg New York Tokyo, pp 77–101Google Scholar
  23. Riederer P, Lange KW (1992) Pathogenesis of Parkinson's disease. Curr Opin Neurol Neurosurg 5: 295–300Google Scholar
  24. Riederer P, Lange KW, Kornhuber J, Danielczyk W (1992) Glutamatergic-dopaminergic balance in the brain. Its importance in motor disorders and schizophrenia. Drug Res 42 (I) Nr 2a: 265Google Scholar
  25. Romeis B (1989) Mikroskopische Technik. Urban & Schwarzenberg, Munich Vienna Baltimore, pp 210–211Google Scholar
  26. Scher W, Scher BM (1992) A possible role for nitric oxide in glutamate (MSG)-induced asthma, “Hot-dog headache”, pugilistic Alzheimer's disease, and other disorders. Med Hypoth 38: 185–188Google Scholar
  27. Scherer-Singler U, Vincent SR, Kimura H, McGeer EG (1983) Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry. J Neurosci Meth 9: 229–234Google Scholar
  28. Schmidt HHHW, Gagne GD, Nakane M, Pollock JS, Miller MF, Murad F (1992a) Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem 40: 1439–1456Google Scholar
  29. Schmidt HHHW, Smith RM, Nakane M, Murad F (1992b) Ca2+/calmodulin-dependent NO synthase type I: a biopteroflavoprotein with Ca2+/calmodulin-independent diaphorase and reductase activities. Biochem 31: 3243–3249Google Scholar
  30. Wolf G, Würdig S, Schünzel G (1992) Nitric oxide synthase in rat brain is predominantly located at neuronal endoplasmatic reticulum: an electron microscopic demonstration of NADPH-diaphorase activity. Neurosci Lett 147: 63–66Google Scholar
  31. Wolf G, Henschke G, Würdig S (1993) Glutamate agonist-induced hippocampal lesion and nitric oxide synthase/NADPH-diaphorase: a light and electron microscopical study in the rat. Neurosci Lett 161: 49–52Google Scholar
  32. Wood PL, Emmett MR, Rao TS, Cler J, Mick S, Iyengar S (1990) Inhibition of Nitric oxide synthase blocks N-methyl-D-aspartate-, Quisqualate-, Kainate-, Harmaline- and Pentylenetetrazole-dependent increases in cerebellar cyclic GMP in vivo J Neurochem 55: 346–348Google Scholar
  33. Würdig S, Wolf G (1994) Localization of NADPH-diaphorase/nitric oxide synthase activity in the rat cerebellar cortex: a light and electron microscopic study. Hirnforsch (in press)Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • R. Böckelmann
    • 1
  • G. Wolf
    • 1
  • G. Ransmayr
    • 2
  • P. Riederer
    • 3
  1. 1.Institute of Medical Neurobiology, Medical FacultyUniversity of MagdeburgMagdeburgFederal Republic of Germany
  2. 2.Department of NeurologyUniversity of InnsbruckAustria
  3. 3.Department of PsychiatryUniversity of WürzburgFederal Republic of Germany

Personalised recommendations