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Effects of manganese exposure and antioxidant therapy on oxidative stress and stereotypic behaviors in rats

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Steven C. Fordahl (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Keith Erikcon

Abstract: Manganese (Mn) is an essential dietary element required for several important physiological processes. However, accumulation of Mn due to excessive environmental exposure is known to pose neurological health concerns that manifest as movement abnormalities and cognitive impairment. Oxidative stress has been hypothesized to play a role in this dysfunction. In these studies we examined the effect Mn exposure had on oxidative stress in the brain with or without antioxidant therapy, and how brain regional Mn accumulation affected stereotypic behaviors in rats. Sprague-Dawley rats raised on AIN-93G diet were randomized into a Mn free group (deionized water) and Mn exposed group (deionized water with 1 g Mn/L). Each group was then subdivided into three additional groups receiving injections of either saline (vehicle) or antioxidant therapy: 200 mg/kg N-acetyl-cysteine (NAC) or 5 mg/kg (-)-epigallocatechin-3-gallate (EGCG) to yield six groups total, each with an n=6. During the sixth week of treatment, stereotypic rat behaviors (total distance traveled, sleep, sniff, and groom) were monitored using Clever Systems Home Cage Scan. Upon completion of the sixth week the rat brains were removed with the caudate putamen (CP) and hippocampus (HC) sectioned out and analyzed for Mn and iron (Fe) concentrations, total glutathione (GSH) levels, lipid peroxidation in the form of F2-Isoprostanes (F2-IsoPs), along with glutathione peroxidase (GPx) and catalase mRNA levels. Results were considered significant when p≤0.05. Mn exposure significantly increased Mn concentrations in both the CP and HC, accompanied by significantly decreased Fe:Mn ratios in Mn-exposed groups. Mn significantly increased total distance traveled in each Mn-exposed group and decreased sniff behavior in the Mn only group. Only modest alterations in GSH and catalase levels were present in each region, although, a significant positive correlation between Mn concentration and GPx mRNA expression was observed. Additionally, F2-IsoP results showed no evidence of increased oxidative damage compared to CN regardless of EGCG or NAC therapy. These data, compared to the body of Mn toxicity research, suggest that oral Mn exposure may not generate deleterious levels of oxidative stress leading to overt neurological dysfunction. This exposure paradigm, instead, may result in subtle neurochemical alterations associated with behavior change and potential cognitive impairment.

Additional Information

Publication
Thesis
Language: English
Date: 2009
Keywords
Behavior, EGCG, Glutathione, Manganese, Neurotoxicity, Oxidative Stress
Subjects
Manganese $x Metabolism.
Oxidative stress.
Manganese $x Toxicology.
Neurotoxic agents.
Cognition disorders.
Glutathione.
Rats $x Behavior $x Research.