Neuronal protective and rescue effects of deprenyl against MPP+ dopaminergic toxicity

  • R. -M. Wu
  • D. L. Murphy
  • C. C. Chiueh
Full Papers

DOI: 10.1007/BF01276865

Cite this article as:
Wu, R.M., Murphy, D.L. & Chiueh, C.C. J. Neural Transmission (1995) 100: 53. doi:10.1007/BF01276865

Summary

Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP+, 2.1–16.8 nmol) dose-dependently injured nigral neurons as reflected by reduced dopamine levels in the ipsilateral striatum four days after the infusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP+ into the substantia nigra protected against MPP+-induced moderate (20–50%) but not severe (over 70%) nigral injury as reflected in striatal dopamine reductions. However, supplementary treatment with deprenyl (0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion of MPP+ significantly rescued nigral neurons from more severe damage caused by a higher MPP+ does (8.4 nmol) manifested by a lesser striatal dopamine decrease (−31%) compared to the non-deprenyl treated group (−70%). Thus, in addition to the blockade of bioactivation of MPTP, deprenyl can protect and/or rescue nigral neurons from MPP+-induced dopaminergic neurotoxicity. These in vivo data add further evidence to suggest that deprenyl, a putative and clinically unproven neuroprotective agent, may be of value in slowing the progressive nigral degeneration in “early” Parkinson's disease, but may prove to be less so in its terminal stages.

Keywords

Deprenyl (selegiline) MPTP MPP+ Parkinson's disease dopamine substantia nigra nigrostriatal neuron 

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • R. -M. Wu
    • 1
    • 3
  • D. L. Murphy
    • 2
  • C. C. Chiueh
    • 1
  1. 1.Unit on Neurotoxicology and NeuroprotectionLaboratory of Clinical Science, National Institute of Mental HealthBethesdaUSA
  2. 2.Section on Clinical NeuropharmacologyLaboratory of Clinical Science, National Institute of Mental HealthBethesdaUSA
  3. 3.Department of NeurologyNational Taiwan University HospitalTaipeiTaiwan