| Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors. | |
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MedLine Citation:
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PMID: 22056924 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 1g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24h 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. |
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Authors:
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Steve Fordahl; Paula Cooney; Yunping Qiu; Guoxiang Xie; Wei Jia; Keith M Erikson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-10-21 |
Journal Detail:
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Title: Neurotoxicology and teratology Volume: 34 ISSN: 1872-9738 ISO Abbreviation: Neurotoxicol Teratol Publication Date: 2012 Jan-Feb |
Date Detail:
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Created Date: 2012-01-30 Completed Date: 2012-10-15 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 8709538 Medline TA: Neurotoxicol Teratol Country: United States |
Other Details:
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Languages: eng Pagination: 27-36 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Behavior, Animal / drug effects*, physiology Brain / blood supply, drug effects*, physiopathology Disease Models, Animal Liver / blood supply, drug effects*, physiopathology Male Manganese / blood, metabolism* Manganese Poisoning / blood, metabolism*, physiopathology Rats Rats, Sprague-Dawley Stereotyped Behavior / drug effects*, physiology Water Pollutants, Chemical / adverse effects*, blood* |
| Grant Support | |
ID/Acronym/Agency:
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R15 NS061309-01/NS/NINDS NIH HHS; R15 NS061309-01/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Water Pollutants, Chemical; 7439-96-5/Manganese |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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