MPTP Parkinsonism in the Cat: Pattern of Neuronal Loss May Partially be Explained by the Distribution of MAO-B in the Brain

  • J. S. Schneider
Conference paper
Part of the Advances in Behavioral Biology book series (ABBI, volume 32)


Recently, it has been shown that administration of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to cats produces a parkinsonian syndrome consisting of akinesia, rigidity, postural tremor, and decreased responsiveness to sensory stimulation (Schneider et al., 1986). While animals eventually recover from this behavioral syndrome (Schneider et al., 1986), the majority of substantia nigra pars compacta (SNc) cells are irreversibly damaged. Tyrosine hydroxylase (TH) immunohistochemistry and cresyl violet Nissl substance staining demonstrate an extensive loss of SNc cells even five months after initial MPTP treatment at a time when the animal appears to have recovered much of its behavioral functions (Schneider and Markham, 1986). While the damage to the SNc is the most prominent feature of the MPTP-induced disorder, other mesencephalic dopamine cell groups also sustain damage. The retrorubral (A-8) dopamine cell group located dorsal to the SNc experiences a much more moderate loss of neurons while the ventral tegmental area (VTA) appears to receive only reversible damage (as evidenced by an acute decrease in TH immunoreactivity within the first few weeks following MPTP administration and an eventual return of staining) (Fig. 1).


Tyrosine Hydroxylase Ventral Tegmental Area Locus Coeruleus Dorsal Raphe Nucleus Ventral Mesencephalon 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bak, I.J., Schneider, J.S., and Markham, C.H., 1986, Early morphological changes in substantia nigra following MPTP administration to the cat, Soc. Neurosci. Abst., 12, in press.Google Scholar
  2. Castagnoli, N., Chiba, K., and Trevor, A.J., 1985, Potential bioactivation pathways for the neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), Life Sci., 36:225–230.PubMedCrossRefGoogle Scholar
  3. Cohen, G., Pasik, P., Cohen, B., Leist, A., Mytilineon, C., and Yahr, M.D., 1985, Pargyline and deprenyl prevent the neurotoxicity of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys, Eur. J. Pharmacol., 106: 209–210.CrossRefGoogle Scholar
  4. Hogan, M.J. and McCauley, R.B., Separation of antigenic determinants and the active site of bovine MAO-B. In Preparation.Google Scholar
  5. Leger, L., Wiklund, L., Descarries, L., and Persson, M., 1979, Description of an idolaminergic cell component in the cat locus coeruleus: A fluorescence histochemical and radioautographic study, Brain Res., 168:43–46.PubMedCrossRefGoogle Scholar
  6. Levitt, P., Pintar, J.E., and Breakfield, X.I., 1982, Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc. Natl. Acad. Sci. USA, &(:6385–6389.Google Scholar
  7. Schneider, J.S. and Markham, C.H., 1986, Neurotoxic effects of N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry, Brain Res., 373:258–267.PubMedCrossRefGoogle Scholar
  8. Schneider, J.S., Yuwiler, A., and Markham, C.H., 1986, Production of a Parkinson-like syndrome in the rat with N-methy1-4-pheny1-1,2,3,6-tetrahydropyridine (MPTP): Behavior, histology, and biochemistry, Exptl. Neurol., 91:293–307.CrossRefGoogle Scholar
  9. Schneider, J.S., Yuwiler, A. and Markham, C.H., Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP. Brain Res., in press.Google Scholar
  10. Shen, R.-S., Abell, C.W., Gessner, W., and Brossi, A., 1985, Serotonergic conversion of MPTP and dopaminergic accumulation of MPP+, FEBS Letters, 189: 225–230.PubMedCrossRefGoogle Scholar
  11. Szabo, J., 1980, Organization of the ascending striatal afferents in monkeys, J. Comp. Neurol., 189:307–321.PubMedCrossRefGoogle Scholar
  12. Uchida, E. and Koelle, G.B., 1984, Histochemical investigation of criterion for the distinction between monoamine oxidase A and B in various species, J. Histochem. Cytochem., 32:667–673.PubMedCrossRefGoogle Scholar
  13. Westlund, K.N., Denney, R.M., Kochersperger, L.M., Rose, R.M., and Abell, C.W., 1985, Distinct monoamine oxidase A and B populations in primate brain, Science, 230:181–183.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • J. S. Schneider
    • 1
  1. 1.Department of NeurologyUCLA School of MedicineLos AngelesUSA

Personalised recommendations