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Nicotinic receptors and Parkinson's disease

Institution: The Parkinson's Institute
Investigator(s): Maryka Quik, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0216 Award: $376,470
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Although tobacco use is generally associated with detrimental health related effects including respiratory disease, cardiovascular disease and cancer, the results from a large series of studies done between 1961 and 2000 show that there is about a 50% decrease in the incidence of Parkinson’s disease in tobacco users. Parkinson’s disease is a relatively common movement disorder which occurs in approximately 1% of the population over 50 years of age and is due to degeneration of dopamine nerve cells in the brain. Treatments available to date involve administration of the dopamine drug L-dopa and/or other drugs which stimulate the dopamine system in the brain. Although quite beneficial in the early stages of the disease, these drugs become less effective with continued treatment. Disease progression is inevitable with immobility and dementia present at the end stages. The development of new approaches is thus essential for Parkinson’s disease management. Our rationale for investigating a role for nicotine stems from recent studies which show that nicotine drug therapy, in combination with l-dopa, may be beneficial in relieving some of the motor and memory difficulties that occur after nigrostriatal degeneration, and furthermore from experimental evidence which shows that nicotine may exert long term protection against nerve cell damage.

The goal of our research is to study nicotinic receptors in brain tissue in an animal model of Parkinson’s disease. Nicotinic receptors are the molecules in the brain that are activated by nicotine. Experimental studies have shown that nicotinic receptors are decreased in some brain areas in Parkinson’s disease. The fact that receptors are decreased in this neurological disorder could suggest that stimulation of the receptors which remain may result in a return of functions somewhat closer to normal. However, when nicotine enters the body either through smoking, or use of the nicotine patch or gum, it stimulates many different types of nicotinic receptor both in the brain and in the rest of the body. Nicotine treatment may therefore result in numerous biological effects in the body, only some of which are desirable or beneficial. For this reason it is important to identify which nicotinic receptors are changed in Parkinson’s disease. Once this is known, it may be possible to develop drugs which act with the receptors that are deficient in Parkinson’s disease, and thus optimize beneficial and minimize negative side effects. To study the receptors that are changed in Parkinson’s disease brain, we will use a number of different experimental techniques and approaches involving drugs and reagents which target nicotinic receptors in different ways. This work may lead to the development of new therapies for the treatment of Parkinson’s disease.
Publications

Declines in different beta-2* containing nicotinic receptor populations in monkey striatum after nigrostriatal damage.
Periodical: Journal of Pharmacology and Experimental Therapeutics Index Medicus:
Authors: Kulak JM, Musachio JL, McIntosh JM, Quik M ART
Yr: 2002 Vol: 303 Nbr: Abs: Pg: 633-639

Differential declines in striatal nicotinic receptor subtype function after nigrostriatal damage in mice.
Periodical: Molecular Pharmacology Index Medicus:
Authors: Quik M, Sum JD, Whiteaker P, McCallum SE, Marks MJ, Musachio JM, McIntosh JM, et al. ART
Yr: 2003 Vol: 63 Nbr: Abs: Pg: 1169-1179

L-Dopa treatment modulates nicotinic receptors in monkey striatum.
Periodical: Molecular Pharmacology Index Medicus:
Authors: Quik M, Bordia T, Okihara M, Fan H, Marks MJ, McIntosh JM, Whiteaker P ART
Yr: 2003 Vol: 64 Nbr: Abs: Pg: 619-628

Differential changes in nicotinic receptor subtypes after nigrostriatal damage in mice.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Sum JD, McIntosh JM, Musachio JL, Quik M ABS
Yr: 2002 Vol: Nbr: Abs: 32 Pg:

Declines in distinct beta-2* nicotinic receptor populations in monkey striatum after nigrostriatal damage.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Kulak JM, McIntosh JM, Musachio JL, Quik M ABS
Yr: 0 Vol: Nbr: Abs: 32 Pg:

L-Dopa treatment modulates nicotinic receptors in monkey striatum
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Bordia T, Okihara M, Fan H, Marks MJ, McIntosh JM, Whiteaker P, Quik M ABS
Yr: 2003 Vol: Nbr: Abs: 33 Pg:

Loss of alpha-conotoxin MII- and A85380-sensitive nicotinic receptors in Parkinson's disease striatum.
Periodical: Journal of Neurochemistry Index Medicus:
Authors: Quik M, Bordia T, Forno L, McIntosh JM ART
Yr: 2004 Vol: 88 Nbr: Abs: Pg: 668-679

I-alpha-conotoxinMII nicotinic receptors after nigrostriatal damage in monkeys.
Periodical: Neuroscience Index Medicus:
Authors: Quik M ART
Yr: 2004 Vol: Nbr: Abs: Pg:

Smoking, nicotine and Parkinson's disease
Periodical: Trends in Neuroscience Index Medicus:
Authors: Qwik M ART
Yr: 2004 Vol: 27 Nbr: Abs: Pg: 561 - 568

Partial recovery of striatal [125I]Conotoxin MII sensitive nicotinic receptors after nigrostriatal damage.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Lai A, Sum J, Okihara M, Fan H, McIntosh JM, Quik M ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Selective downregulation of striatal alpha-conotoxinMII nicotinic receptor sites and function with chronic oral nicotine administration.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Lai A, Parameswaran N, Fan H, McIntosh JM, Grady S, Quik M ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Regionally-specific reduction in alpha-conotoxinMII-sensitive [3H]dopamine release in monkey striatum following nigrostriatal damage.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: McCallum SE, Parameswaran N, Bordia T, Lai A, McIntosh JM, Grady SR, Quik M ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Nicotinic receptor subunit composition in monkey striatum; changes with MPTP and l-dopa treatment.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Bordia T, Gotti C, Vailati S, Clementi F, Fan H, McIntosh JM, Quik M ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Selective recovery of striatal 1-alpha-conotoxinMII nicotinic receptors after nigrostriatal damage in monkeys.
Periodical: Neuroscience Index Medicus:
Authors: Lai A, Sum J, Fan H, McIntosh MJ, Quik M ART
Yr: 2004 Vol: 127 Nbr: Abs: Pg: 399 - 408

Subunit composition of nicotinic receptors in monkey striatum; effect of MPTP and L-dopa treatments.
Periodical: Molecular Pharmacology Index Medicus:
Authors: Quik M, Vailati S, Bordia T, Kulak JM, Fan H, McIntosh JM Clementi F, Cotti C ART
Yr: 2005 Vol: 67 Nbr: Abs: Pg: 32 - 41

Decrease in a3*/a6* nicotinic receptors but not nicotine-evoked dopamine release in monkey brain after nigrostrialtal damage.
Periodical: Molecular Pharmacology Index Medicus:
Authors: McCallum SE, Parameswaran N, Bordia T, McIntosh JM, Grady SR, Quik M ART
Yr: 0 Vol: Nbr: Abs: Pg:

The in vivo imaging ligand Iodo-A-85380 and radiolabeled epibatidine bind to similar nicotinic receptor sites in human control and parkinson's disease brains in vitro.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Quik M, Okihara M, Forno L, Musachio J ABS
Yr: 0 Vol: Nbr: Abs: 32 Pg: