MPP + Induced Substantia Nigra Degeneration Is Attenuated in nNOS Knockout Mice

MPP + Induced Substantia Nigra Degeneration Is Attenuated in nNOS Knockout Mice Recent studies showed that neuronal nitric oxide synthase (nNOS) plays a role in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. In the present study we examined the effects of striatal injection of 1-methyl-4-phenylpyridinium (MPP + ) on substantia nigra degeneration in mutant mice lacking the nNOS gene or the endothelial nitric oxide synthase (eNOS) gene. Both striatal lesion volume and substantia nigra degeneration were significantly attenuated in the nNOS mutant mice but not in the eNOS mutant mice. The mice lacking nNOS showed a significant attenuation of MPP + -induced increases of 3-nitrotyrosine concentrations in the striatum. In a separate experiment administration of 7-nitroindazole for 48 h after MPP + injections significantly attenuated substantia nigra degeneration in rats. Immunohistochemical studies showed apposition of nNOS-positive neuronal processes on tyrosine hydroxylase-positive neurons. These results provide further evidence that neuronally derived NO and peroxynitrite play a role in MPP + neurotoxicity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurobiology of Disease Elsevier

MPP + Induced Substantia Nigra Degeneration Is Attenuated in nNOS Knockout Mice

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Publisher
Elsevier
Copyright
Copyright © 1997 Academic Press
ISSN
0969-9961
eISSN
1095-953X
DOI
10.1006/nbdi.1997.0141
Publisher site
See Article on Publisher Site

Abstract

Recent studies showed that neuronal nitric oxide synthase (nNOS) plays a role in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. In the present study we examined the effects of striatal injection of 1-methyl-4-phenylpyridinium (MPP + ) on substantia nigra degeneration in mutant mice lacking the nNOS gene or the endothelial nitric oxide synthase (eNOS) gene. Both striatal lesion volume and substantia nigra degeneration were significantly attenuated in the nNOS mutant mice but not in the eNOS mutant mice. The mice lacking nNOS showed a significant attenuation of MPP + -induced increases of 3-nitrotyrosine concentrations in the striatum. In a separate experiment administration of 7-nitroindazole for 48 h after MPP + injections significantly attenuated substantia nigra degeneration in rats. Immunohistochemical studies showed apposition of nNOS-positive neuronal processes on tyrosine hydroxylase-positive neurons. These results provide further evidence that neuronally derived NO and peroxynitrite play a role in MPP + neurotoxicity.

Journal

Neurobiology of DiseaseElsevier

Published: Jan 1, 1997

References

  • Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage
    Iadecola, C.; Zhang, F.; Xu, X.
  • Pyramidal neurones in pathological human motor cortex express nitric oxide synthase
    Wallace, M.N.; Tayebjee, M.H.; Rana, F.S.; Farquhar, D.A.; Nyong, A.O.
  • Induction of nitric oxide synthase and motoneuron death in newborn and early postnatal rats following spinal root avulsion
    Wu, Y.; Li, Y.; Liu, H.; Wu, W.

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