title: Regional cerebral metabolism in mouse under chronic manganese exposure: implications for manganism.
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.
authors: NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
authors: Puneet
authors: P
authors: Bagga
authors: Anant Bahadur
authors: AB
authors: Patel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D015636:Magnesium Chloride / Q000633:toxicity*; D008297:Male; D020149:Manganese Poisoning / Q000378:metabolism* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015636:Magnesium Chloride