Related Experiment Video
Updated: Mar 3, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Subchronic, Low-Level Intraperitoneal Injections of Manganese (IV) Oxide and Manganese (II) Chloride Affect Rat Brain
Brian S Nielsen1, Erik H Larsen2, Ole Ladefoged3
11 Environment and Toxicology, DHI, Hørsholm, Denmark.
Abstract:
Manganese (Mn) is neurotoxic and can induce manganism, a Parkinson-like disease categorized as being a serious central nervous system irreversible neurodegenerative disease. An increased risk of developing symptoms of Parkinson disease has been linked to work-related exposure, for example, for workers in agriculture, horticulture, and people living near areas with frequent use of Mn-containing pesticides. In this study, the focus was placed on neurochemical effects of Mn. Rats were dosed intraperitoneally with 0.9% NaCl (control), 1.22 mg Mn (as MnO2)/kg bodyweight (bw)/day, or 2.5 mg Mn (as MnCl2)/kg bw/day for 7 d/wk for 8 or 12 weeks. This dosing regimen adds relevant new knowledge about Mn neurotoxicity as a consequence of low-dose subchronic Mn dosing. Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid, and the activity of acetylcholinesterase changed. Importantly, a target parameter for Parkinson disease and manganism, the striatal DA concentration, was reduced after 12 weeks of dosing with MnCl2. Plasma prolactin concentration was not significantly affected due to a potentially reduced dopaminergic inhibition of the prolactin release from the anterior hypophysis. No effects on the striatal α-synuclein and synaptophysin protein levels were detected.
Insights
Low-dose manganese exposure in rats caused neurochemical changes and reduced dopamine, a key indicator in Parkinson disease and manganism. This study highlights risks associated with subchronic manganese toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Manganese (Mn) is a neurotoxic metal linked to Parkinson-like symptoms (manganism).
- Occupational and environmental exposures to manganese increase Parkinson disease risk.
- Subchronic low-dose manganese exposure effects on neurochemistry require further investigation.
Purpose of the Study:
- To investigate the neurochemical consequences of subchronic low-dose manganese exposure in a rat model.
- To assess the impact of manganese on neurotransmitter levels and acetylcholinesterase activity in specific brain regions.
- To evaluate manganese's effect on dopamine levels, a critical marker for Parkinson disease and manganism.
Main Methods:
- Rats were administered low doses of manganese (MnO2 or MnCl2) or saline intraperitoneally for 8 or 12 weeks.
- Manganese concentrations were measured in brain regions (striatum, rest of brain) and plasma.
- Neurotransmitter concentrations (noradrenaline, dopamine, glutamate, etc.) and acetylcholinesterase activity were analyzed.
Main Results:
- Manganese levels increased in the striatum, brain, and plasma following exposure.
- Significant alterations in regional brain neurotransmitter concentrations and acetylcholinesterase activity were observed.
- Striatal dopamine levels were reduced after 12 weeks of MnCl2 dosing, a key finding for Parkinson disease and manganism.
Conclusions:
- Subchronic low-dose manganese exposure induces significant neurochemical changes in rats.
- Reduced striatal dopamine levels indicate a potential mechanism for manganese-induced neurodegeneration.
- Further research is needed to understand the long-term implications of manganese exposure on neurological health.
