ToxSci Advance Access originally published online on January 4, 2007
Toxicological Sciences 2007 97(2):428-437; doi:10.1093/toxsci/kfl199
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Developmental Exposure to Methylmercury Alters Learning and Induces Depression-like Behavior in Male Mice
* Division of Toxicology and Neurotoxicology
Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, S171 77 Stockholm, Sweden
Department of Neuroscience, Karolinska Institutet, S171 77 Stockholm, Sweden
School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705
1 To whom correspondence should be addressed at Division of Toxicology and Neurotoxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, S171 77 Stockholm, Sweden. Fax: +46 8 329041. E-mail: sandra.ceccatelli{at}ki.se.
Received November 7, 2006; accepted December 20, 2006
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Abstract |
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To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5–15 and 26–36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.
Key Words: developmental neurotoxicity; behavior; neural stem cells.
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