Genetic and Toxin-induced Depletion of Striatal Dopamine
Idiopathic Parkinson’s disease is not heritable, though some neurological disorders leading to parkinsonian symptoms are known to have a genetic base (Agid et al. 1986). The discovery of MPTP-induced parkinsonism has reinforced the view that environmental toxins, rather than heritable factors, are involved in the etiology of Parkinson’s disease. We nevertheless wish to emphasize in this chapter that in terms of its neuropathology as expressed in the dopamine-containing systems, there is an inherited disease that displays a remarkable resemblance to Parkinson’s disease, and also to other parkinsonian disorders including 1-methyl-4-phenyl-1,2,5,6-tetrohydropyridine (MPTP)-induced parkinsonism. This genetic disease is carried in the weaver mouse as an autosomal recessive mutation, the consequences of which include defects in the dopamine-containing systems of the brain (Schmidt et al. 1982, Roffler-Tarlov and Graybiel 1984). The following summary is based on work over the past five years, during which we have noted remarkable similarities between the effects of the weaver gene and those reported for MPTP administered to normal adult mice. The similarities and differences need to be explored more formally in parallel investigations and will be. However the purpose of this chapter is to compare the key features of the damage resulting from the administration of the toxin MPTP with that induced by the weaver gene. The effects of MPTP have been studied in many species following the initial observations of parkinsonian effects in man (Davis et al. 1979; Langston et al. 1983). Here, discussion will be confined to the consequences of MPTP treatment of mice so that species variations will not intervene.
KeywordsStriatal Dopamine MPTP Treatment Nigrostriatal System Dopamine Content Dopaminergic Neurotoxicity
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