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Role of nicotine/nicotinic receptors in Parkinson's disease

Institution: The Parkinson's Institute
Investigator(s): Maryka Quik, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0015 Award: $644,770
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
The long term goal of the work in our laboratory is to study the sites in the brain that are stimulated by nicotine. Nicotine is one of the major chemicals in cigarette smoke and thought to be important for many of the effects of smoking on the brain and nerve tissue. The sites in brain and other nerve tissue which are stimulated by nicotine are called nicotinic receptors. We are especially interested in studying the changes which occur in these receptors in neurological disorders such as Parkinson's disease. This is a devastating disease which affects approximately 1% of the population over the age of 50. The symptoms of this disease include difficulty in initiating actions, in walking, talking, swallowing and maintaining posture, as well as other movement problems. The reason we are interested in studying the nicotinic receptors in relation to Parkinson's disease is because previous research has suggested that some of the movement problems experienced by Parkinson patients are less severe after smoking a cigarette, chewing nicotine gum or using the nicotine patch. As well, nicotine may help to lessen memory difficulties which occur in some people with Parkinson's disease. Research also suggests that Parkinson's disease occurs less frequently in people who smoke or use other tobacco products, and that it is nicotine which is responsible for these positive effects. The number of nicotinic receptors are decreased in the brains of people who have Parkinson's disease. The nicotine in cigarette smoke, in the nicotine patch or in gum may lead to an extra stimulation of these remaining nicotinic receptors. We would like to know how nicotine has these positive effects. However, work to understand how nicotine works is complicated by the fact that there are many different kinds of nicotinic receptors in the brain and in nerve tissue. Nicotine stimulates all of these receptors which can help overcome some of the problems associated with Parkinson's disease but which also can cause many undesirable side effects on the heart, the blood vessels and stomach, to name only a few. Our aim is to determine which specific nicotinic receptors are affected in Parkinson's disease To study this, we will use an animal models. It is important to know which nicotinic receptors are changed in Parkinson's disease, because this will allow us to synthesize drugs which act only with the receptors that are affected. This research will help us to develop drugs which reduce the movement problems in Parkinson's disease without producing the numerous undesirable side effects which frequently also occur with nicotine. The effects of smoking/nicotine may therefore point to the development of new therapies to treat neurological diseases such as Parkinson's disease.
Publications

Alterations in nicotinic receptor subunit mRNA levels in monkey brain after MPTP treatment
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Polonskaya Y, Gillespie A, Jakowec M, Lloyd GK, Langston JW ABS
Yr: 1999 Vol: 25 Nbr: Abs: Pg: 188

Differential alterations in nicotinic receptor apha6 and beta3 subunit mRNAs in monkey substantia nigra after nigrostriatal degeneration
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Polonskaya Y, Gillespie A, Lloyd GK, Langston JW ART
Yr: 2000 Vol: 100 Nbr: Abs: Pg: 63-72

Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization
Periodical: Journal of Comparative Neurology Index Medicus:
Authors: Quik M, Polonskaya Y, Gillespie A, Jankowec M, Lloyd GK, Langston JW ART
Yr: 2000 Vol: 425 Nbr: Abs: Pg: 58-69

Vulnerability of I-conotoxin MII sites to nigrostriatal damage in monkey
Periodical: Journal of Neuroscience Index Medicus:
Authors: Quik M, Polonskaya Y, Kulak J, McIntosh JM ART
Yr: 2001 Vol: 21 Nbr: Abs: Pg: 5494 - 5500

Differential alterations in non-alpha7 and alpha7 nicotinic receptors in monkey striatum after MPTP treatment
Periodical: Neuroscience Index Medicus:
Authors: Kulak JM, Quik M ABS
Yr: 2000 Vol: 26 Nbr: Abs: 1 Pg: 526

Decline in alpha3 containing nicotinic receptors in monkey stratum after nigrostriatal degeneration
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Polanskaya Y, McIntosh JM ABS
Yr: 2000 Vol: 26 Nbr: Abs: 2 Pg: 526

Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits.
Periodical: Pharmacological Reviews Index Medicus:
Authors: Lukas RJ, Changeux JP, Le Novere N, et al. ART
Yr: 1999 Vol: 51 Nbr: Abs: Pg: 397 - 401

Nicotinic receptors and parkinson's disease
Periodical: European Journal of Pharmacology Index Medicus:
Authors: Quik M, and Jeyarasasingam G ART
Yr: 2000 Vol: 393 Nbr: Abs: Pg: 223 - 230

Loss of nicotinic receptors in monkey striatum after MPTP treatment is due to a decline in alpha-conotoxin MII sites.
Periodical: Molecular Pharmacology Index Medicus:
Authors: Kulak JM, McIntosh JM, and Quik M ART
Yr: 2002 Vol: 61 Nbr: Abs: Pg: 230 - 238

Differential nicotinic receptor expression in monkey basal ganglia; effects of nigrostriatal damage.
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Polonskaya Y, McIntosh JM, and Kulak JM ART
Yr: 2002 Vol: 112 Nbr: Abs: Pg: 619 - 630

Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic receptors as well as alpha4beta2 subtypes.
Periodical: Journal of Neurochemistry Index Medicus:
Authors: Kulak JM, Sum J, Musachio JL, McIntosh JM, and Quik M ART
Yr: 2002 Vol: 81 Nbr: Abs: Pg: 403 - 406

Nicotine and nicotinic receptors; relevance to parkinson's disease.
Periodical: Neurotoxicology Index Medicus:
Authors: Quik M, and Kulak JM ART
Yr: 2002 Vol: 131 Nbr: Abs: Pg: 1 - 14

Declines in differenct beta2 containi8ng 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, and Quik M ART
Yr: 0 Vol: Nbr: Abs: Pg:

Localization of nicotinic receptor subunit mRNAs in monkey brain by in situ hybridization.
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Jakoqec M, Polonskaya Y, Gillespie A, Lloyd GK, and Langston JW ABS
Yr: 1998 Vol: 24 Nbr: Abs: Pg: 1947

Alpha-conotoxin MII sensitive nicotinic receptors are selectively decreased in the caudate-putamen of parkinsonian monkeys.
Periodical: Neuroscience Index Medicus:
Authors: Kulak JM, McIntosh JM, and Quik M ABS
Yr: 2001 Vol: 31 Nbr: Abs: 10 Pg: 240

Similar expression pattern of alpha-conotoxin MII sites and the dopamine transporter in control and MPTP lesioned monkey basal ganglia.
Periodical: Neuroscience Index Medicus:
Authors: Quik M, Polonskaya Y, Kulak J, and McIntosh JM ABS
Yr: 2001 Vol: 31 Nbr: Abs: 2 Pg: 487

Declines in distinct beta2 nicotinic receptor populations in monkey striatum after nigrostriatal damage.
Periodical: Neuroscience Index Medicus:
Authors: Kulak JM, McIntosh JM, Musachio JL, and Quik M ABS
Yr: 2002 Vol: 32 Nbr: Abs: Pg: