The aims of the proposed studies are: I) To evaluate the antiparkinsonian effectiveness of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibitors in monkeys with hemiparkinsonian symptoms elicited by unilateral intracarotid administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) and to study morphological and biochemical changes in the residual dopamine (DA) neurons following MPTP lesions. These studies will evaluate the potentiation of the antiparkinsonian effects of L-dopa by deprenyl and by other MAO and COMT inhibitors. The effects of deprenyl on the integrity of the residual DA neurons following MPTP-induced nigrostriatal DA degeneration will be investigated. 2) To determine in rodents the compensatory changes of the residual DA neurons and of the postsynaptic DA receptors following lesioning with MPTP or 6- hydroxydopamine (6OH-DA). These studies will complement our investigations in monkeys by assessing the compensatory changes in pre- and postsynaptic DA neurons following MPTP- or 6OH-DA-induced lesions in rodents. The issue whether compensatory changes elicited by neurotoxic lesions are altered by chronic treatment with the MAO and COMT inhibitors and whether these alterations are beneficial or detrimental to the therapeutic response will be investigated. 3) To evaluate whether chronic treatment with ganglioside GM1 ameliorates the parkinsonian symptoms in monkeys with MPTP-induced parkinsonism and whether GM1 exerts neuroprotective action. The effects of combined treatment of GM1 with deprenyl on morphological and biochemical adaptations of the residual nigrostriatal DA neurons in monkeys with MPTP- induced hemiparkinsonism will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS006801-25
Application #
2260200
Study Section
Neurology A Study Section (NEUA)
Project Start
1977-08-01
Project End
1998-04-30
Budget Start
1995-05-08
Budget End
1996-04-30
Support Year
25
Fiscal Year
1995
Total Cost
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
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