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Role of nicotine in neuro protection

Institution: The Parkinson's Institute
Investigator(s): Maryka Quik, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8RT-0105 Award: $722,263
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Tobacco use is usually associated with detrimental effects on health, such as an increased susceptibility to cardiovascular disease and cancer. In contrast to these negative findings, however, it appears that tobacco use may have beneficial effects in Parkinson's disease. Over 35 epidemiological studies, done over a 40 year period, report a lower incidence of Parkinson's disease in tobacco users. This includes users of cigarettes, cigars and chewing tobacco. The component in tobacco, which is responsible for this beneficial effect in Parkinson's disease, has not been identified. However, experimental studies suggest that it may be the nicotine in tobacco because it is known to interact with the same system in brain, which degenerates in Parkinson's disease. Parkinson's disease is a movement disorder, in which there is severe slowness of movement, rigidity and tremor. It occurs in approximately 1% of the population over 50 years of age. In Parkinson's disease there is a degeneration of specific brain areas, which contain a compound called dopamine. It is not known why these brain areas degenerate. Current treatments for Parkinson's disease involve drugs that are very useful in the initial stages of the disease. However, these drugs only treat the symptoms of Parkinson's disease. They do not prevent the disease from progressing. The goal of our research is to understand why smoking decreases the incidence of Parkinson's disease. As mentioned earlier, there is experimental evidence, which suggests that nicotine is involved in this beneficial effect of tobacco. As a way to study this possibility, we will do experiments to identify the molecules in brain that nicotine interacts with to prevent degeneration of nerve cells. Once we know how nicotine works in the brain and prevents Parkinson's disease, it will be possible to design specific drugs to prevent this debilitating movement disorder. Tobacco use is usually associated with detrimental effects on health, such as an increased susceptibility to cardiovascular disease and cancer. In contrast to these negative findings, however, it appears that tobacco use may have beneficial effects in Parkinson's disease. Over 35 epidemiological studies, done over a 40 year period, report a lower incidence of Parkinson's disease in tobacco users. This includes users of cigarettes, cigars and chewing tobacco. The component in tobacco, which is responsible for this beneficial effect in Parkinson's disease, has not been identified. However, experimental studies suggest that it may be the nicotine in tobacco because it is known to interact with the same system in brain, which degenerates in Parkinson's disease. Parkinson's disease is a movement disorder, in which there is severe slowness of movement, rigidity and tremor. It occurs in approximately 1% of the population over 50 years of age. In Parkinson's disease there is a degeneration of specific brain areas, which contain a compound called dopamine. It is not known why these brain areas degenerate. Current treatments for Parkinson's disease involve drugs that are very useful in the initial stages of the disease. However, these drugs only treat the symptoms of Parkinson's disease. They do not prevent the disease from progressing. The goal of our research is to understand why smoking decreases the incidence of Parkinson's disease. As mentioned earlier, there is experimental evidence, which suggests that nicotine is involved in this beneficial effect of tobacco. As a way to study this possibility, we will do experiments to identify the molecules in brain that nicotine interacts with to prevent degeneration of nerve cells. Once we know how nicotine works in the brain and prevents Parkinson's disease, it will be possible to design specific drugs to prevent this debilitating movement disorder.
Publications

Nicotine induced neuroprotection against MPP+ toxicity is mediated through a non-alpha7 receptor
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasigam G, Devendrarao N, Quik M ABS
Yr: 2000 Vol: 26 Nbr: Abs: 18 Pg: 280

Nicotine administration reduces striatal MPP+ levels in mice.
Periodical: Brain Research Index Medicus:
Authors: Quik M and Mi Monte DA ART
Yr: 2001 Vol: 917 Nbr: Abs: Pg: 219-224

Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons of MPP+ induced toxicity in culture.
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasingam G, Tompkins L, and Quck M ART
Yr: 2002 Vol: 109 Nbr: Abs: Pg: 275-285

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 and Quik M ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

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

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

Nicotine and nicotinic receptors; relevance to Parkinson's disease
Periodical: Neurotoxicology Index Medicus:
Authors: Quik M, Kulak JM ART
Yr: 2002 Vol: 131 Nbr: Abs: Pg: 581-594

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, Fan H, Marks MJ, McIntosh JM, Whiteaker P ART
Yr: 0 Vol: Nbr: Abs: Pg:

alpha-conotoxin MII sensitive nicotinic receptors are selectively decreased in the caudate-putamen of parkinsonian monkeys
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Kulak JM, McIntosh JM, Quik M ABS
Yr: 31 Vol: Nbr: 240.10 Abs: Pg:

Similar expression pattern of alpha-conotoxin MII sites and the dopamine transporter in control and MPTP lesioned monkey basal ganglia
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Quik M, Polonskaya Y, Kulak J, McIntosh JM ABS
Yr: 31 Vol: Nbr: 487.2 Abs: Pg:

Declines in distinct beta2 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: 32 Vol: Nbr: Abs: Pg:

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: 33 Vol: Nbr: Abs: 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: 33 Vol: Nbr: Abs: Pg:

Nicotine partially protects dopaminergic cells from MPP neurotoxicity in vitro.
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasingam G, Quik M ABS
Yr: 1999 Vol: 25 Nbr: Abs: Pg: 333

Nicotine induced neuroprotection against MPP+ toxicity is mediated through a non-alpha7 receptor
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasigam G, Devendrarao N, Quik M ABS
Yr: 2000 Vol: 26 Nbr: Abs: 18 Pg: 280

Nicotine administration reduces striatal MPP+ levels in mice.
Periodical: Brain Research Index Medicus:
Authors: Quik M and Mi Monte DA ART
Yr: 2001 Vol: 917 Nbr: Abs: Pg: 219-224

Stimulation of non-alpha7 nicotinic receptors partially protects dopaminergic neurons of MPP+ induced toxicity in culture.
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasingam G, Tompkins L, and Quck M ART
Yr: 2002 Vol: 109 Nbr: Abs: Pg: 275-285

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 and Quik M ABS
Yr: 2002 Vol: Nbr: Abs: Pg:

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

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

Nicotine and nicotinic receptors; relevance to Parkinson's disease
Periodical: Neurotoxicology Index Medicus:
Authors: Quik M, Kulak JM ART
Yr: 2002 Vol: 131 Nbr: Abs: Pg: 581-594

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, Fan H, Marks MJ, McIntosh JM, Whiteaker P ART
Yr: 0 Vol: Nbr: Abs: Pg:

alpha-conotoxin MII sensitive nicotinic receptors are selectively decreased in the caudate-putamen of parkinsonian monkeys
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Kulak JM, McIntosh JM, Quik M ABS
Yr: 31 Vol: Nbr: 240.10 Abs: Pg:

Similar expression pattern of alpha-conotoxin MII sites and the dopamine transporter in control and MPTP lesioned monkey basal ganglia
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Quik M, Polonskaya Y, Kulak J, McIntosh JM ABS
Yr: 31 Vol: Nbr: 487.2 Abs: Pg:

Declines in distinct beta2 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: 32 Vol: Nbr: Abs: Pg:

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: 33 Vol: Nbr: Abs: 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: 33 Vol: Nbr: Abs: Pg:

Nicotine partially protects dopaminergic cells from MPP neurotoxicity in vitro.
Periodical: Neuroscience Index Medicus:
Authors: Jeyarasasingam G, Quik M ABS
Yr: 1999 Vol: 25 Nbr: Abs: Pg: 333