Intranasal administration of sodium dimethyldithiocarbamate induces motor deficits and dopaminergic dysfunction in mice
Autor: | Débora Lanznaster, Tainara M. Moura, Carla I. Tasca, Franciane Bobinski, Anicleto Poli, Josiel Mileno Mack, Caio M. Massari, Luiz Felipe de Souza, Roger Walz, Richard L. Doty, Ariana Ern Schmitz, Tuane Bazanella Sampaio, Rui Daniel Prediger, Alcir Luiz Dafre |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Parkinson's disease Tyrosine 3-Monooxygenase Dopamine Central nervous system Hypothermia Pharmacology Motor Activity Toxicology Dimethyldithiocarbamate 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Neurochemical Medicine Animals Parkinson Disease Secondary Administration Intranasal Tyrosine hydroxylase business.industry General Neuroscience Dopaminergic medicine.disease Olfactory Bulb Corpus Striatum Apomorphine Oxidative Stress 030104 developmental biology medicine.anatomical_structure chemistry business Reactive Oxygen Species 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Neurotoxicology. 66 |
ISSN: | 1872-9711 |
Popis: | The primary etiology of Parkinson’s disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervous system from the nasal mucosa via the olfactory nerves. To address this issue, we evaluated the effects of 1, 2 or 4 days of intranasal (i.n., 1 mg/nostril/day) infusions of sodium dimethyldithiocarbamate (NaDMDC), a dimethyldithiocarbamate more soluble than ziram, on locomotor activity in the open field, neurological severity score and rotarod performance. We also addressed the effects of four daily i.n. NaDMDC infusions on olfactory bulb (OB) and striatal measures of cell death, reactive oxygen species (ROS), tyrosine hydroxylase, and the levels of dopamine, noradrenaline, serotonin, and their metabolites. A single i.n. administration of NaDMDC did not significantly alter the behavioral measures. Two consecutive days of i.n. NaDMDC administrations led to a transient neurological deficit that spontaneously resolved within a week. However, the i.n. infusions of NaDMDC for 4 consecutive days induced motor and neurological deficits for up to 7 days after the last NaDMDC administration and increased striatal TH immunocontent and dopamine degradation within a day of the last infusion. Pharmacological treatment with the anti-parkinsonian drugs l -DOPA and apomorphine improved the NaDMDC-induced locomotor deficits. NaDMDC increased serotonin levels and noradrenaline metabolism in the OB 24 h after the last NaDMDC infusion, ROS levels in the OB 2 h after the last infusion, and striatum 2 and 24 h after the last infusion. These results demonstrate, for the first time, that i.n. NaDMDC administration induces neurobehavioral and neurochemical impairments in mice. This accords with evidence that dimethyldithio-carbamate exposure increases the risk of PD and highlights the possibility that olfactory system could be a major route for NaDMDC entry to central nervous system. |
Databáze: | OpenAIRE |
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