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Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Alterations in brain dopamine and GABA following inorganic or organic manganese administration
Abstract:
Administration of manganese to mice in the form of MnCl2 (4%) in the diet for 6 months or injections of the organic fuel-additive methylcyclopentadienyl manganese tricarbonyl (MMT) for 3 weeks resulted in a decrease in dopamine concentrations in the striatum and olfactory tubercles. The GABA content of the striatum was elevated after either treatment while the cerebellar GABA content did not change; GABA in the substantia nigra of MMT-treated mice was also increased. Choline acetyltransferase activity remained unchanged in response to either manganese treatment. These results are in general agreement with previous studies of inorganic manganese toxicity in other animal species. These changes in neurotransmitter concentrations were observed after longterm manganese administration but were not seen in mice injected acutely with MMT or exposed to MnCl2 for 1-2 months.
Insights
Long-term exposure to manganese, including MnCl2 and methylcyclopentadienyl manganese tricarbonyl (MMT), altered neurotransmitter levels. Dopamine decreased, while GABA increased in specific brain regions, indicating potential neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Manganese is an essential element, but excessive exposure can lead to neurotoxicity.
- Previous studies have indicated that inorganic manganese can affect neurotransmitter systems.
Purpose of the Study:
- To investigate the neurochemical effects of chronic exposure to inorganic manganese (MnCl2) and an organic manganese fuel additive (MMT) in mice.
- To compare the impact of different forms and durations of manganese exposure on brain neurotransmitter concentrations.
Main Methods:
- Mice were administered MnCl2 in their diet for 6 months or MMT via injection for 3 weeks.
- Neurotransmitter levels (dopamine, GABA) and enzyme activity (choline acetyltransferase) were measured in specific brain regions (striatum, olfactory tubercles, cerebellum, substantia nigra).
- Acute and sub-chronic exposure groups were also included for comparison.
Main Results:
- Chronic administration of both MnCl2 and MMT led to decreased dopamine concentrations in the striatum and olfactory tubercles.
- Elevated GABA levels were observed in the striatum following both treatments, and in the substantia nigra after MMT exposure.
- No significant changes in choline acetyltransferase activity were detected.
- Neurotransmitter alterations were associated with long-term exposure, not acute or sub-chronic exposure.
Conclusions:
- Chronic exposure to manganese, whether inorganic or organic, can induce significant changes in brain neurotransmitter systems, particularly dopamine and GABA.
- These findings align with previous research on inorganic manganese toxicity and highlight the potential neurotoxic effects of MMT.
- The observed neurochemical changes underscore the importance of considering the duration and form of manganese exposure when assessing neurotoxic risk.
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