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Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Fordahl, Steve ; Cooney, Paula ; Qiu, Yunping ; Xie, Guoxiang ; Jia, Wei ; Erikson, Keith M

Neurotoxicology and teratology, 2012-01, Vol.34 (1), p.27-36 [Periódico revisado por pares]

New York, NY: Elsevier Inc

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Título:
Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors
Autor: Fordahl, Steve ; Cooney, Paula ; Qiu, Yunping ; Xie, Guoxiang ; Jia, Wei ; Erikson, Keith M
Assuntos: Animals ; Behavior ; Behavior, Animal - drug effects ; Behavior, Animal - physiology ; Biological and medical sciences ; Biomarker ; Brain - blood supply ; Brain - drug effects ; Brain - physiopathology ; Chemical and industrial products toxicology. Toxic occupational diseases ; Circadian rhythm ; Disease Models, Animal ; Emergency ; Liver - blood supply ; Liver - drug effects ; Liver - physiopathology ; Male ; Manganese ; Manganese - blood ; Manganese - metabolism ; Manganese Poisoning - blood ; Manganese Poisoning - metabolism ; Manganese Poisoning - physiopathology ; Medical Education ; Medical sciences ; Metabolomics ; Metals and various inorganic compounds ; Neurotoxicity ; Rats ; Rats, Sprague-Dawley ; Stereotyped Behavior - drug effects ; Stereotyped Behavior - physiology ; Toxicology ; Water Pollutants, Chemical - adverse effects ; Water Pollutants, Chemical - blood
É parte de: Neurotoxicology and teratology, 2012-01, Vol.34 (1), p.27-36
Descrição: Abstract Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography–time of flight–mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague–Dawley rats had access to deionized drinking water either Mn-free or containing 1 g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24 h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, − 14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.
Editor: New York, NY: Elsevier Inc
Idioma: Inglês

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Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

Fordahl, Steve ; Cooney, Paula ; Qiu, Yunping ; Xie, Guoxiang ; Jia, Wei ; Erikson, Keith M

New York, NY: Elsevier Inc

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