title: Vanadium exposure induces olfactory dysfunction in an animal model of metal neurotoxicity.
abstract: Epidemiological evidence indicates chronic environmental exposure to transition metals may play a role in chronic neurodegenerative conditions such as Parkinson's disease (PD). Chronic inhalation exposure to welding fumes containing metal mixtures may be associated with development of PD. A significant amount of vanadium is present in welding fumes, as vanadium pentoxide (V2O5), and incorporation of vanadium in the production of high strength steel has become more common. Despite the increased vanadium use in recent years, the neurotoxicological effects of this metal are not well characterized. Recently, we demonstrated that V2O5 induces dopaminergic neurotoxicity via protein kinase C delta (PKCδ)-dependent oxidative signaling mechanisms in dopaminergic neuronal cells. Since anosmia (inability to perceive odors) and non-motor deficits are considered to be early symptoms of neurological diseases, in the present study, we examined the effect of V2O5 on the olfactory bulb in animal models. To mimic the inhalation exposure, we intranasally administered C57 black mice a low-dose of 182μg of V2O5 three times a week for one month, and behavioral, neurochemical and biochemical studies were performed. Our results revealed a significant decrease in olfactory bulb weights, tyrosine hydroxylase (TH) levels, levels of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and increases in astroglia of the glomerular layer of the olfactory bulb in the treatment groups relative to vehicle controls. Neurochemical changes were accompanied by impaired olfaction and locomotion. These findings suggest that nasal exposure to V2O5 adversely affects olfactory bulbs, resulting in neurobehavioral and neurochemical impairments. These results expand our understanding of vanadium neurotoxicity in environmentally-linked neurological conditions.
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors.forename: Hilary Afeseh
authors.initials: HA
authors.lastname: Ngwa
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors.forename: Arthi
authors.initials: A
authors.lastname: Kanthasamy
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors.forename: Huajun
authors.initials: H
authors.lastname: Jin
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.
authors.forename: Vellareddy
authors.initials: V
authors.lastname: Anantharam
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA. Electronic address: akanthas@iastate.edu.
authors.forename: Anumantha G
authors.initials: AG
authors.lastname: Kanthasamy
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000209:etiology; D020258:Neurotoxicity Syndromes / Q000150:complications*; D000857:Olfaction Disorders / Q000209:etiology*; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D014131:Trace Elements / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017968:Vanadium Compounds / Q000633:toxicity*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014131:Trace Elements; D017968:Vanadium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; C066075:vanadium pentoxide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Neurotoxicity; Non-motor symptoms; Olfactory system; Parkinson's disease; Risk assessment; Vanadium