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Published on: October 4, 2021
L-DOPA treatment reverses the motor alterations induced by manganese exposure as a Parkinson disease experimental
Jose Luis Ordoñez-Librado1, Veronica Anaya-Martinez, Ana Luisa Gutierrez-Valdez
1Laboratorio de Neuromorfologia, FES Iztacala, UNAM, Av. de los Barrios 1, Tlalnepantla 54090, Mexico.
Abstract:
This investigation was designed to determine whether l-DOPA treatment improves the motor alterations observed after divalent and trivalent manganese (Mn) mixture inhalation on mice to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of 0.04 M manganese chloride (MnCl(2)) and manganese acetate (Mn(OAc)(3)), 1h twice a week for 5 months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. Overall behavior was assessed by ratings and by videotaped analyses; by the end of Mn exposure period, 10 mice were orally treated with 7.5mg/kg L-DOPA. After 5 months of Mn-mixture inhalation striatal dopamine content decreased 71%, mice developed evident deficits in motor performance manifested as akinesia, postural instability and action tremor; these alterations were reverted with L-DOPA treatment. Our results suggest that the motor alterations induced by the inhalation of the combination of MnCl(2)/Mn(OAc)(3) are related to nigrostriatal dopaminergic function providing new light on the understanding of manganese neurotoxicity as a suitable Parkinson disease experimental model.
Insights
Manganese inhalation caused motor deficits in mice by decreasing dopamine. L-DOPA treatment reversed these Parkinson-like symptoms, suggesting manganese neurotoxicity impacts dopaminergic pathways.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Manganese (Mn) exposure is linked to neurological disorders.
- Dopaminergic system dysfunction is implicated in motor control deficits.
Purpose of the Study:
- To investigate if L-DOPA can ameliorate motor impairments caused by manganese inhalation.
- To confirm the dopaminergic origin of manganese-induced motor alterations.
Main Methods:
- Mice inhaled a manganese chloride and manganese acetate mixture for 5 months.
- Motor function tests were conducted weekly.
- Dopamine levels were measured, and L-DOPA treatment was administered to a subset of mice.
Main Results:
- Manganese inhalation significantly decreased striatal dopamine by 71%.
- Mice exhibited akinesia, postural instability, and tremor.
- L-DOPA treatment successfully reverted these motor deficits.
Conclusions:
- Inhaled manganese mixture induces motor impairments related to nigrostriatal dopaminergic dysfunction.
- L-DOPA effectively reverses manganese-induced motor deficits.
- This study provides a potential Parkinson's disease experimental model for understanding manganese neurotoxicity.
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