Effects of MPTP on Nigrostriatal and Mesolimbic Dopaminergic Systems in Young and Aged Mice
Parkinson’s disease is a slowly progressive neurodegenerative disorder that seldom occurs in patients below the age of sixty. It is characterized by decreased dopamine in the striatum and a loss of pigmented dopamine neurons in the substantia nigra pars compacta (Forno, 1982; Hornykiewicz, 1982). However, in addition to degeneration of this nigrostriatal system, other monoamine systems also degenerate including the dopaminergic ventral tegmental area, the noradrenergic locus coeruleus system, the cholinergic nucleus basalis system, and the cholinergic dorsal motor nucleus of the vagus (Alvord et al., 1974; Burns et al., 1984; Greenfield and Bosanquet, 1953; Whitehouse et al., 1983). Furthermore, decreased levels of norepinephrine and serotonin and their metabolites in the cerebrospinal fluid have been reported in patients with Parkinson’s disease (Burns et al., 1983; Hornykiewicz, 1982). Normal aging, in the absence of a neurodegenerative disorder, also has been associated with a decline of dopamine levels in the striatum, although the age related decline is more gradual than the decline seen in patients with Parkinson’s disease. Substantia nigra neurons diminish in number with age, leading to decreased synthesis and levels of dopamine in terminal striatal fields (McGeer et al., 1977). Thus, the Parkinson patient appears to have a rapid neurodegenerative process superimposed on top of this age-related decline in the dopaminergic nigrostriatal system.
KeywordsToxicity Dopamine Tyrosine Dementia Serotonin
Unable to display preview. Download preview PDF.
- Forno, L.S., 1982, Pathology of Parkinson’s disease, in: “Movement Disorders,” C.D. Marsden and S. Fahn, ed., Butterworth and Company, London.Google Scholar
- Hornykiewicz, O., 1982, Brain neurotarnsmitter changes in Parkinson’s disease, in: “Movement Disorders,” C.D. Marsden and S. Fahn, ed., Butterworth and Company, London.Google Scholar
- Alvord, E.C.,Jr., Forno, L.S., Kusske, J.A., Kauffman, R.J., Rhodes, J.S., and Goetowski, C.R., 1974, The pathology of Parkinsonism: A comparison of degenerations in cerebral cortex and brain stem, in: “Second Canadian-American Cinference on Parkinson’s disease,” Advances in Neurology, Vol. 5, F.M. McDowel and A. Barbeau, ed., Raven Press, New York.Google Scholar
- Burns, R.S., Markey, S.P., Phillips, J.M., and Chiueh, C.C., 1984, The neurotoxicity of 1-methyl-4-phenyl-l,2,3, 6-tetrahydropyridine in the monkey and man, Can. J. Neurol., 11:166.Google Scholar
- Gupta, M., Feiten, D.L., and Feiten, 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, ed., Academic Press, New York.Google Scholar