This study was supported by grants Schu 932/3-1 and K1 782/3-1 from the Deutsche Forschungsgemeinschaft (to J.B.S.).

  • 1
    Banati R.B., Daniel S.E., Blunt S.B. (1998) Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease.Mov. Disord. 13 2 21227.
  • 2
    Beal M.F. (1995) Aging, energy and oxidative stress in neurodegenerative diseases.Ann. Neurol. 38 3 57366.
  • 3
    Bloem B.R., Irwin I., Buruma O.J.S., Haan J., Roos R.A.C., Tetrud J.W., Langston J.W. (1990) The MPTP model: versatile contributions to the treatment.J. Neurol. Sci. 97 2 73293.
  • 4
    Bredt D.S., Glatt C.E., Hwang P.M., Fotuhi M., Dawson T.M., Snyder S.H. (1991) Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase.Neuron 7 6 15624.
  • 5
    Di Monte D.A., Royland J.E., Anderson A., Castagnoli K., Castagnoli N.J, Langston J.W. (1997) Inhibition of monoamine oxidase contributes to the protective effect of 7-nitroindazole against MPTP neurotoxicity.J. Neurochem. 69 1 7711773.
  • 6
    Franklin K.B.J. & Paxinos G. (1996) The Mouse Brain in Stereotaxic Coordinates. Academic Press, Sydney.
  • 7
    Gonzalez-Scarano F. & Baltuch C. (1999) Microglia as mediators of inflammatory and degenerative diseases.Annu. Rev. Neurosci. 22 2 19240.
  • 8
    Good P.F., Hsu A., Werner P., Perl D.P., Olanow C.W. (1998) Protein nitration in Parkinson's disease.J. Neuropathol. Exp. Neurol. 57 3 38342.
  • 9
    Hantraye P., Brouillet E., Ferrante R., Palfi S., Dolan R., Matthews R.T., Beal M.F. (1996) Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons.Nat. Med. 2 1 0171021.
  • 10
    Heneka M.T., Löschmann P., Gleichmann M., Weller M., Schulz J.B., Wüllner U., Klockgether T. (1998) Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-α/lipopolysaccharide. J. Neurochem. 71 8 894.
  • 11
    Hirsch E.C., Hunot S., Damier P., Faucheux B. (1998) Glial cells and inflammation in Parkinson's disease: a role in neurodegeneration?Ann. Neurol. 44 (Suppl.) , S115S120.
  • 12
    Hunot S., Boissiere F., Faucheux B., Brugg B., Mouatt-Prigent A., Agid Y., Hirsch E.C. (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson's disease.Neuroscience 72 3 55363.
  • 13
    Hunot S., Dugas N., Faucheux B., Hartmann A., Tardieu M., Debre P., Agid Y., Dugas B., Hirsch E.C. (1999) FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells.J. Neurosci. 19 3 4403447.
  • 14
    Langston J.W., Forno L.S., Tetrud J., Reeves A.G., Kaplan J.A., Karluk D. (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure.Ann. Neurol. 46 5 98605.
  • 15
    Laubach V.E., Shesely E.G., Smithies O., Sherman P.A. (1995) Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death.Proc. Natl. Acad. Sci. USA 92 1 068810692.
  • 16
    Liberatore G.T., Jackson-Lewis V., Vukosavic S., Mandir A.S., Vila M., McAuliffe W.G., Dawson V.L., Dawson T.M., Przedborski S. (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease.Nat. Med. 5 1 4031409.
  • 17
    Matthews R.T., Yang L., Beal M.F. (1997) S-Methylthiocitrulline, a neuronal nitric oxide synthase inhibitor, protects against malonate and MPTP neurotoxicity. Exp. Neurol. 143 2 82286.
  • 18
    Moore P.K., Wallace P., Gaffen Z., Hart S.L., Babbedge R.C. (1993) Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovacular effects.Br. J. Pharmacol. 110 2 19224.
  • 19
    Pennathur S., Jackson-Lewis V., Przedborski S., Heinecke J.W. (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and O,O′-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson's disease. J. Biol. Chem. 274 3 462134628.
  • 20
    Przedborski S., Jackson-Lewis V., Yokoyama R., Shibata T., Dawson V.L., Dawson T.M. (1996) Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity.Proc. Natl. Acad. Sci. USA 93 4 5654571.
  • 21
    Schulz J.B., Matthews R.T., Beal M.F. (1995a) Role of nitric oxide in neurodegenerative diseases.Curr. Opin. Neurol. 8 4 80486.
  • 22
    Schulz J.B., Matthews R.T., Muqit M.M.K., Browne S.E., Beal M.F. (1995b) Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice.J. Neurochem. 64 9 36939.
  • 23
    Tatton N.A. & Kish S.J. (1997) In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining.Neuroscience 77 1 0371048.
  • 24
    Tipton K.F. & Singer T.P. (1993) Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds.J. Neurochem. 61 1 1911206.