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Effects of manganese on the nervous system
Abstract:
The acute effect of manganese on the synaptosomal sodium-dependent choline uptake was studied. Manganese (Mn) revealed a mixed competitive-noncompetitive inhibition of the choline uptake, at Mn concentrations in the mM range. We do not believe that lack of choline for transmitter synthesis is of importance in Mn poisoning. Manganese chloride intubation of neonatal rats resulted in reduced homovanillic acid content in the striatum and hypothalamus. No other alteration in the dopamine or serotonin metabolism was revealed. A mechanism of cytotoxic action of manganese is discussed in terms of its transition metal properties and interaction with reactive oxygen compounds which result in the production of substances that alkylate or oxidize the cellular thiols.
Insights
Manganese inhibits choline uptake in brain synaptosomes. Manganese poisoning in neonatal rats reduced homovanillic acid, suggesting impacts on dopamine metabolism, not serotonin.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Manganese (Mn) is an essential trace element, but excessive exposure can lead to neurotoxicity.
- Choline uptake is crucial for acetylcholine synthesis, a key neurotransmitter.
- Understanding Mn's impact on neurotransmitter systems is vital for diagnosing and treating Mn poisoning.
Purpose of the Study:
- To investigate the acute effects of manganese on sodium-dependent choline uptake in synaptosomes.
- To examine the impact of manganese chloride on dopamine and serotonin metabolism in neonatal rats.
- To elucidate the cytotoxic mechanisms underlying manganese neurotoxicity.
Main Methods:
- In vitro studies of synaptosomal sodium-dependent choline uptake kinetics with varying Mn concentrations.
- Intubation of neonatal rats with manganese chloride followed by biochemical analysis of brain tissue.
- Assessment of homovanillic acid, dopamine, and serotonin levels in striatum and hypothalamus.
Main Results:
- Manganese exhibited mixed competitive-noncompetitive inhibition of choline uptake at millimolar concentrations.
- Manganese chloride administration led to decreased homovanillic acid in neonatal rat striatum and hypothalamus.
- No significant alterations were observed in dopamine or serotonin metabolism.
Conclusions:
- Choline uptake inhibition by manganese is unlikely to be the primary cause of Mn poisoning.
- Manganese neurotoxicity may involve alterations in dopamine metabolism, specifically impacting homovanillic acid levels.
- Manganese's cytotoxic effects are proposed to stem from its transition metal properties and interaction with reactive oxygen species, leading to cellular thiol damage.