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Waterborne Manganese Exposure Alters Plasma, Brain, and Liver Metabolites Accompanied by Changes in Stereotypic Behaviors

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Paula Cooney, Departmental Research Staff (Creator)
Keith M. Erikson, Associate Professor and Director of Graduate Studies (Creator)
Steven C. Fordahl (Creator)
Wei Jia, Professor and Co-Director of the UNCG Center for Research Excellence in Bioactive Food Components (Creator)
Yunping Qiu, Post Doctoral Fellow, Center for Research Excellence in Bioactive Food Components (Creator)
Guoxiang Xie, Post Doctoral Fellow, Center for Research Excellence in Bioactive Food Components (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

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.

Additional Information

Publication
Neurotoxicology and Teratology, 34(1), 27-36
Language: English
Date: 2012
Keywords
manganese, metabolomics, biomarker, neurotoxicity, behavior, circadian rhythm