Cyclosporin a Enhances Neurotoxicity of N-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in Mice

  • Masako Hagihara
  • Kenichiro Fujishiro
  • Akira Takahashi
  • Makoto Naoi
  • Toshiharu Nagatsu
Part of the Advances in Behavioral Biology book series (ABBI, volume 38A)


N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known neurotoxin that elicits symptoms very similar to those seen Parkinsonism in humansl,2 and causes specific neurodegeneration in the nigro-striatal system in primates 3 and rodents.4 The molecular basis of the neurotoxicity of MPTP has been extensively studied.5,6 Recently we reported that activities of tyrosine hydroxylase [tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC, TH] and L-3,4dihydroxyphenylalanine decarboxylase (aromatic L-amino acid decarboxylase, aromatic L-amino acid carboxylyase, EC were markedly redugpd in the striatum of C57BL/6N mice after 8 days of MPTP administration.7 In addition, a marked reduction in dopamine (DA) content was observed in the striatum. On the other hand, cerebrospinal fluid obtained frog Parkinsonian patients showed a marked reduction in beta 2-microglobulin,8 which suggests that some disorder of the immune system may be involved in the pathogenesis of Parkinsonism. The present study was undertaken to study the effect of cyclosporin A (CsA), an immune suppressor, on the toxicity of MPTP to assess the contribution of the immune system to the pathological changes seen in the dopaminergic and noradrenergic systems in parkinsonism.


Tyrosine Hydroxylase Dopaminergic Neuron Herpes Simplex Virus Infection Parkinsonian Patient Dihydroxyphenylalanine Decarboxylase 
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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Masako Hagihara
    • 1
  • Kenichiro Fujishiro
    • 2
  • Akira Takahashi
    • 2
  • Makoto Naoi
    • 1
  • Toshiharu Nagatsu
    • 1
  1. 1.Department of BiochemistryNagoya University School of MedicineNagoyaJapan
  2. 2.Department of NeurologyNagoya University School of MedicineNagoyaJapan

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