Degenerative Risks for Parkinson's Disease After Toxin Exposure and Stress
Annual rept. 1 Jul 1999-1 Jul 2000
FINCH UNIV OF HEALTH SCIENCES/CHICAGO MEDICAL SCHOOL IL
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Parkinsons disease PD is caused by deterioration of the dopamine DA nigrostriatal system. Loss of DA can be induced specifically by neurotoxic lesion of DA neurotransmitter producing somata in the substantia nigra, or through lesioning DA terminals in the striatum with subsequent degeneration in substantia nigra. Characterization of an animal model of PD after bilateral intrastriatal infusions of the neurotoxin 6-hydroxydopamine has been initiated in the first period of this project. Different doses of the neurotoxin in multiple striatal infusion sites were tested, and treated animals were followed for two months. Behavioral assessments of the motor impairments produced by the neurotoxin treatment were evaluated using the Montoya staircase apparatus for skilled reaching to evaluate dexterity and motor sequencing ability in the forepaws. It was determined that this apparatus also assessed posture and balance abilities. This reduced the number of procedures needed to examine behavioral deficits in neurotoxin treated animals. Neurochemical analysis of residual striatal DA four weeks following neurotoxin infusion is being determined using HPLC of the DA and its metabolites. Morphological examination of the extent of the losses in striatal DA terminals and DA receptor subtypes will be established in neurotoxin-lesioned brains that are presently stored and awaiting analysis.
- Medicine and Medical Research