UBC Theses and Dissertations
Parkinson's disease : etiology, prevention and treatment Tabatabaei, Ali Reza
This thesis consists of three chapters dealing with different aspects of Parkinson's disease (PD). 3-Acetylpyridine (3-AP), a naturally occurring neurotoxin, was studied for its neurodegenerative properties on the mesostriatal dopaminergic system in rats as a possible environmental cause of idiopathic PD. Chronic administration of this compound to rats caused a moderate but insignificant reduction of striatal dopamine (determined by HPLC measurement of striatal dopamine) and a more substantial degeneration of cerebellar neurons and their neurotransmitters (determined by amino acid analysis of cerebellum). Prophylactic use of a high dose of nicotinamide prevented the reduction of dopamine in the striatum as well as the severe behavioural manifestations induced by 3-AP in rats. The cerebellar damage, however, was not affected. Different mechanisms of damage by 3-AP in these structures were presumed based on the protective effects of nicotinamide in the substantia nigra but not in the cerebellum. Possible protective properties of MK-801 (a noncompetitive NMDA antagonist) and nicotinamide against MPTP neurotoxicity were also examined in mice. MK-801 treatment provided a substantial protection against MPTP-induced reduction of striatal dopamine. Nicotinamide on the other hand provided no such protection. Finally, a new controversial approach to the treatment of parkinsonism was evaluated. Nervous tissue from 13-15 day-old fetuses was transplanted into MPTP-treated mice. The transplanted material was harvested from different areas of the fetal brain and was prepared by various procedures to examine the possible bases of any improvement in the host animal. After two studies, we did not find a biochemical improvement in transplanted mice treated with MPTP regardless of the nature of the transplanted materials.
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