title: Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.
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 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.
authors: Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
authors: Steve
authors: S
authors: Fordahl
authors: Paula
authors: P
authors: Cooney
authors: Yunping
authors: Y
authors: Qiu
authors: Guoxiang
authors: G
authors: Xie
authors: Wei
authors: W
authors: Jia
authors: Keith M
authors: KM
authors: Erikson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008345:Manganese / Q000097:blood / Q000378:metabolism*; D020149:Manganese Poisoning / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D014874:Water Pollutants, Chemical / Q000009:adverse effects* / Q000097:blood*
chemical_list: D014874:Water Pollutants, Chemical; D008345:Manganese