ToxSci Advance Access originally published online on October 7, 2009
Toxicological Sciences 2009 112(2):394-404; doi:10.1093/toxsci/kfp220
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Age-Dependent Susceptibility to Manganese-Induced Neurological Dysfunction
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* Department of Environmental and Radiological Health Sciences, Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523
Trace Element Research Laboratory, Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas 77843
1 To whom correspondence should be addressed at Department of Environmental and Radiological Health Sciences, Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1680 Campus Delivery, Fort Collins, CO 80523-1680. Fax: (970) 491-7569. E-mail: ron.tjalkens{at}colostate.edu.
Received June 30, 2009; accepted August 27, 2009
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Abstract |
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Chronic exposure to manganese (Mn) produces a spectrum of cognitive and behavioral deficits associated with a neurodegenerative disorder resembling Parkinson’s disease. The effects of high-dose exposure to Mn in occupational cohorts and in adult rodent models of the disease are well described but much less is known about the behavioral and neurochemical effects of Mn in the developing brain. We therefore exposed C57Bl/6 mice to Mn by intragastric gavage as juveniles, adults, or both, postulating that mice exposed as juveniles and then again as adults would exhibit greater neurological and neurochemical dysfunction than mice not preexposed as juveniles. Age- and sex-dependent vulnerability to changes in locomotor function was detected, with juvenile male mice displaying the greatest sensitivity, characterized by a selective increase in novelty-seeking and hyperactive behaviors. Adult male mice preexposed as juveniles had a decrease in total movement and novelty-seeking behavior, and no behavioral changes were detected in female mice. Striatal dopamine levels were increased in juvenile mice but were decreased in adult preexposed as juveniles. Levels of Mn, Fe, and Cu were determined by inductively coupled plasma-mass spectrometry, with the greatest accumulation of Mn detected in juvenile mice in the striatum, substantia nigra (SN), and cortex. Only modest changes in Fe and Cu were detected in Mn-treated mice, primarily in the SN. These results reveal that developing mice are more sensitive to Mn than adult animals and that Mn exposure during development enhances behavioral and neurochemical dysfunction relative to adult animals without juvenile exposure.
Key Words: manganese; development; behavior; neurochemistry; metals.