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.
Waterborne Manganese Exposure Alters Plasma, Brain, and Liver Metabolites Accompanied by Changes in Stereotypic Behaviors
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Created on 6/21/2012
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Additional Information
- Publication
- Neurotoxicology and Teratology, 34(1), 27-36
- Language: English
- Date: 2012
- Keywords
- manganese, metabolomics, biomarker, neurotoxicity, behavior, circadian rhythm