Dopaminergic Neurons in the Substantia Nigra in Normal Aging and MPTP-Lesioned Mice

  • Madi Gupta
  • Bhupendra Kishore Gupta
Conference paper
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Parkinson’s disease is a slowly progressive neurodegenerative disorder that seldom occurs in patients below the age of 60. Its incidence increases with age, but the cause remains unknown. Typically, the disease is characterized by decreased dopamine levels in the striatum and a loss of pigmented dopamine nerve cells in the substantia nigra pars compacta. 1-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is a commercially available compound that has been illicitly used as a new type of heroin (Langston et al, 1983). Many users developed a Parkinson-like disorder with bradykinesia, rigidity, tremor, flexed posture, loss of postural reflexes, mutism, and drooling following intravenous (IV) administration of MPTP (Davis et al., 1979; Langston et al., 1983; Langston and Ballard, 1985). Since then, MPTP has been shown to produce parkinsonian symptoms and neuropathology of the nigrostriatal dopamine system in nonhuman primates as well as in mice (Burns et al., 1983; Langston et al., 1985; Heikkila et al., 1984; Gupta et al., 1984–1986).

Keywords

Sucrose Dopamine Tyrosine Neurol Catecholamine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Benedetti, M. S., and Keane, P. E., 1980, Differential changes in monoamine oxidase A and B activity in the aging rat brain, J. Neurochem. 35: 1026–1032.PubMedCrossRefGoogle Scholar
  2. Burns, R. S., Chiueh, C. C., Markey, S. P., Ebert, M. H., Jacobowitz, D. M., and Kopin, I. J., 1983, A primate model of Parkinsonism—Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by MPTP, Proc. Natl. Acad. Sci. USA 80: 4546–4550.PubMedCrossRefGoogle Scholar
  3. Carlsson, A., and Winblad, B., 1976, Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia, J. Neural Transm. 38: 271–276.PubMedCrossRefGoogle Scholar
  4. Davis, G. C., Williams, A. C., Markey, S. P., Ebert, M. H., Caine, E. D., Reichert, C. M., and Kopin, I. J., 1979, Chronic Parkinsonism secondary to intravenous injection of meperidine analogues, Psychiatry Res. 1: 249–254.PubMedCrossRefGoogle Scholar
  5. Finch, C. E., 1973, Catecholamine metabolism in the brains of aging male mice, Brain Res. 52: 261–276.PubMedCrossRefGoogle Scholar
  6. Gupta, M., Felten, D. L., and Gash, D. M., 1984, MPTP alters central catecholamine neurons in addition to the nigrostriatal system, Brain Res. Bull. 13: 737–742.PubMedCrossRefGoogle Scholar
  7. Gupta, M., Felten, D. L., and Felten, S. Y., 1985, MPTP alters monoamine levels in systems other than the nigrostriatal dopaminergic system in mice, in: MPTP—A Neurotoxin Producing a Parkinsonian Syndrome ( S. P. Markey, N. Castagnoli, Jr., A. J. Trevor, and I. J. Kopin, eds.), Academic, Orlando, Florida, pp. 399–402.Google Scholar
  8. Gupta, M., Gupta, B. K., Thomas, R., Bruemmer, V., Sladek, J. R., Jr., and Felten, D. L., 1986, Aged mice are more sensitive to MPTP treatment than young adults, Neurosci. Lett. 70: 326–331.PubMedCrossRefGoogle Scholar
  9. Gupta, M., Felten, D. L., and Ghetti, B., 1987, Selective loss of monoaminergic neurons in weaver mutant mice—An immunocytochemical study, Brain Res. 402: 379–382.PubMedCrossRefGoogle Scholar
  10. Heikkila, R. E., Hess, A., and Duvoisin, R. C., 1984, Dopaminergic neurotoxicity of MPTP in mice, Science 224: 1451–1453.PubMedCrossRefGoogle Scholar
  11. Langston, J. W., and Ballard, P., 1985, Parkinsonism induced by MPTP: Implications for treatment and the pathogenesis of Parkinson’s disease, Can. J. Neurol. Sci. 11: 160–165.Google Scholar
  12. Langston, J. W., Ballard, P., Tetrud, J., and Irwin, I., 1983, Chronic Parkinsonism in humans due to a product of meperidine analog synthesis, Science 219: 979–980.PubMedCrossRefGoogle Scholar
  13. Langston, J. W., Langston, E. B., and Irwin, I., 1985, MPTP induced Parkinsonism in human and non- human primates—Clinical and experimental aspects, Acta Neurol. Scand. 70 (suppl. 100): 49–54.Google Scholar
  14. McGeer, P. L., McGeer, E. G., and Suzuki, J. A., 1977, Aging and extrapyramidal function, Arch. Neurol. 34: 33–35.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Madi Gupta
    • 1
  • Bhupendra Kishore Gupta
    • 1
  1. 1.Department of Anatomical Sciences and NeurobiologyUniversity of Louisville School of MedicineLouisvilleUSA

Personalised recommendations