title: Nicotine increases lifespan and rescues olfactory and motor deficits in a Drosophila model of Parkinson's disease.
abstract: Drosophila melanogaster is an attractive model of familial Parkinson's disease, as flies with loss-of-function mutations of the parkin gene exhibit many pathologies observed in PD patients. Progressive motor deficits found in homozygous parkin mutants seem to result from mitochondrial pathology that causes indirect flight muscle and dopaminergic neuronal degeneration [1,2]. We have found that heterozygous parkin mutants have decreased lifespan, generally progressive motor dysfunction and olfactory deficits compared to control flies, suggesting that mutation of this gene produces a dominant phenotype. Tobacco smokers are dose-dependently less likely to develop PD [3,4]; subsequent in vitro and in vivo studies show that nicotine is protective in models of sporadic PD [6]. Literature addressing the potential protection by nicotine in Parkin loss-of-function models spans limited concentrations and selected time points in the organism's lifespan. We have found that parkin heterozygotes have late-onset climbing and flying deficits as well as decreased viability and olfactory deficits that precede motor defects. While chronic nicotine exposure decreases lifespan and climbing and flying abilities in control flies, it can improve viability and flying capability as well as rescue climbing and olfactory deficits in parkin heterozygotes. Dopaminergic neurons are spared in the parkin heterozygote, perhaps because this phenotype is less severe than in the homozygous parkin mutants. Nicotine pretreatment may be protective in sporadic PD patients and models; however, timely diagnosis remains to be an obstacle. Our results suggest that nicotine also may be protective in familial PD patients, who can be easily identified before motor symptoms occur.
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, United States.
authors.forename: Raegan P
authors.initials: RP
authors.lastname: Chambers
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Call
authors.forename: David
authors.initials: D
authors.lastname: Meyer
authors.forename: Justin
authors.initials: J
authors.lastname: Smith
authors.forename: Jared A
authors.initials: JA
authors.lastname: Techau
authors.forename: Krista
authors.initials: K
authors.lastname: Pearman
authors.forename: Lori M
authors.initials: LM
authors.lastname: Buhlman
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D005426:Flight, Animal / Q000502:physiology; D007150:Immunohistochemistry; D008017:Life Expectancy; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D000857:Olfaction Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D012727:Sex Characteristics; D012903:Smell / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: AR-JP; Drosophila; Drosophila that express wild-type park; Drosophila with heterozygous Parkin loss-of-function mutation; Nicotine; PD; Parkin; Parkinson; Parkinson's disease; SEM; TH; autosomal recessive-juvenile parkinsonism; park(25) het; standard error of the mean; tyrosine hydroxylase; w(1118), control