Document Detail

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.
MedLine Citation:
PMID:  22056924     Owner:  NLM     Status:  MEDLINE    
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.
Steve Fordahl; Paula Cooney; Yunping Qiu; Guoxiang Xie; Wei Jia; Keith M Erikson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-21
Journal Detail:
Title:  Neurotoxicology and teratology     Volume:  34     ISSN:  1872-9738     ISO Abbreviation:  Neurotoxicol Teratol     Publication Date:    2012 Jan-Feb
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-10-15     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8709538     Medline TA:  Neurotoxicol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-36     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Behavior, Animal / drug effects*,  physiology
Brain / blood supply,  drug effects*,  physiopathology
Disease Models, Animal
Liver / blood supply,  drug effects*,  physiopathology
Manganese / blood,  metabolism*
Manganese Poisoning / blood,  metabolism*,  physiopathology
Rats, Sprague-Dawley
Stereotyped Behavior / drug effects*,  physiology
Water Pollutants, Chemical / adverse effects*,  blood*
Grant Support
R15 NS061309/NS/NINDS NIH HHS; R15 NS061309-01/NS/NINDS NIH HHS; R15 NS061309-01/NS/NINDS NIH HHS
Reg. No./Substance:
0/Water Pollutants, Chemical; 42Z2K6ZL8P/Manganese

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