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Updated: May 27, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Regional cerebral metabolism in mouse under chronic manganese exposure: implications for manganism
Puneet Bagga1, Anant Bahadur Patel
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
Abstract:
Chronic manganese (Mn) exposure in rodents, non-human primates and humans has been linked to Parkinson's disease like condition known as Manganism. Mn being a cofactor for many enzymes in brain has been known to be accumulated in various regions differentially and thus exert toxic effect upon chronic overexposure. In present study, neuropathology of Manganism was investigated by evaluating regional neuronal and astroglial metabolism in mice under chronic Mn exposure. Male C57BL6 mice were treated with MnCl(2) (25 mg/kg, i.p.) for 21 days. Cerebral metabolism was studied by co-infusing [U-(13)C(6)]glucose and [2-(13)C]acetate, and monitoring (13)C labeling of amino acids in brain tissue extract using (1)H-[(13)C] and (13)C-[(1)H]-NMR spectroscopy. Glutamate, choline, N-acetyl aspartate and myo-inositol were found to be reduced in thalamus and hypothalamus indicating a loss in neuronal and astroglial cells due to Mn neurotoxicity. Reduced labeling of Glu(C4) from [U-(13)C(6)]glucose and [2-(13)C]acetate indicates an impairment of glucose oxidation by glutamatergic neurons and glutamate-glutamine neurotransmitter cycle in cortex, striatum, thalamus-hypothalamus and olfactory bulb with chronic Mn exposure. Additionally, reduced labeling of Gln(C4) from [2-(13)C]acetate indicates a decrease in acetate oxidation by astroglia in the same regions. However, GABAergic function was alleviated only in thalamus-hypothalamus. Our findings indicate that chronic Mn impairs excitatory (glutamatergic) function in the majority of regions of brain while inhibitory (GABAergic) activity is perturbed only in basal ganglia.
Insights
Chronic manganese (Mn) exposure impairs brain cell metabolism, affecting neuronal and astroglial functions. This study reveals Mn neurotoxicity disrupts excitatory pathways more broadly than inhibitory ones.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Chronic manganese (Mn) exposure is linked to Parkinson's-like symptoms (Manganism).
- Mn accumulates in the brain, potentially causing neurotoxicity.
- Understanding Mn's impact on neuronal and astroglial metabolism is crucial.
Purpose of the Study:
- To investigate the neuropathology of Manganism by assessing regional neuronal and astroglial metabolism in mice under chronic Mn exposure.
- To elucidate the specific metabolic pathways affected by Mn neurotoxicity.
Main Methods:
- Male C57BL6 mice were administered MnCl2 (25 mg/kg) for 21 days.
- Cerebral metabolism was analyzed using co-infused [U-(13)C(6)]glucose and [2-(13)C]acetate.
- 13C labeling of amino acids was monitored via NMR spectroscopy.
Main Results:
- Reduced levels of glutamate, choline, N-acetyl aspartate, and myo-inositol in thalamus and hypothalamus indicate neuronal and astroglial loss.
- Impaired glucose and acetate oxidation in glutamatergic neurons and astroglia across multiple brain regions.
- Alleviation of GABAergic function was specific to the thalamus-hypothalamus.
Conclusions:
- Chronic manganese exposure impairs excitatory (glutamatergic) neurotransmission in most brain regions.
- Inhibitory (GABAergic) activity is perturbed primarily in the basal ganglia.
- Mn neurotoxicity differentially affects neuronal and astroglial metabolism, contributing to Manganism's pathology.
