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Mechanism of Manganese Dysregulation of Dopamine Neuronal Activity
- Source :
- J Neurosci
- Publication Year :
- 2020
- Publisher :
- Society for Neuroscience, 2020.
-
Abstract
- Manganese exposure produces Parkinson’s-like neurological symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or how it regulates the activity of dopamine neurons. Ourin vivostudies suggest manganese accumulates in dopamine neurons of the ventral tegmental area and substantia nigra via nifedipine-sensitive Ca2+channels. Manganese produces a Ca2+channel-mediated current which increases neurotransmitter release and rhythmic firing activity of dopamine neurons. These increases are prevented by blockade of Ca2+channels and depend on downstream recruitment of Ca2+-activated potassium channels to the plasma membrane. These findings demonstrate the mechanism of manganese-induced dysfunction of dopamine neurons, and reveal a potential therapeutic target to attenuate manganese-induced impairment of dopamine transmission.Significance StatementManganese is a trace element critical to many physiological processes. Overexposure to manganese is an environmental risk factor for neurological disorders such as a Parkinson’s disease-like syndrome known as manganism. We found manganese dose-dependently increased the excitability of dopamine neurons, decreased the amplitude of action potentials, and narrowed action potential width. Blockade of Ca2+channels prevented these effects as well as manganese accumulation in the mouse midbrainin vivo. Our data provide a potential mechanism for manganese-regulation of dopaminergic neurons.
- Subjects :
- 0301 basic medicine
Male
Parkinson's disease
Action Potentials
Substantia nigra
Neurotransmission
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Organ Culture Techniques
Dopamine
medicine
Manganism
Premovement neuronal activity
Animals
Humans
Neurotransmitter
Research Articles
Cells, Cultured
Manganese
Dose-Response Relationship, Drug
General Neuroscience
Dopaminergic Neurons
Dopaminergic
medicine.disease
Potassium channel
Ventral tegmental area
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
HEK293 Cells
chemistry
nervous system
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- J Neurosci
- Accession number :
- edsair.doi.dedup.....a868b19aa1796da542d5d60bf7f72ac1