ToxSci Advance Access originally published online on May 22, 2009
Toxicological Sciences 2009 110(2):389-400; doi:10.1093/toxsci/kfp105
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Methylmercury Speciation Influences Brain Gene Expression and Behavior in Gestationally-Exposed Mice Pups
* National Institute of Nutrition and Seafood Research, 5817 Bergen, Norway
School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand
Nutritional Sciences Division
Anatomy and Human Sciences, School of Biomedical and Health Sciences, King's College London, SE1 9NH UK
1 To whom correspondence should be addressed at Chris Glover, Biology Building, School of Biological Sciences, University of Canterbury, Ilam, Christchurch 8140, New Zealand. Fax: +64-3-364-2590. E-mail: chris.glover{at}canterbury.ac.nz.
Received March 27, 2009; accepted May 15, 2009
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Abstract |
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The greatest source of human exposure to methylmercury (MeHg) is the diet, in particular the consumption of seafood. To investigate the importance of dietary MeHg speciation on neurotoxicity, balb/c mice dams were exposed to MeHgCys (the naturally-occurring salt) and MeHgCl (the laboratory salt), at concentrations up to 4.5 mg/kg, for 11 weeks (inclusive of 3 weeks gestational and 2 weeks post-partum exposure). Impacts of developmental exposure were assessed in their offspring by monitoring transcriptomic (brain gene expression via microarray and quantitative PCR), tissue mercury (Hg) accumulation, and neurobehavioral endpoints. There were no differences in tissue Hg accumulation between the two forms of MeHg presented, but differences in pup behavior and gene expression endpoints were noted. For example, MeHgCl, but not MeHgCys, impaired pup activity in an open field assessment. Similar impacts of MeHgCl were noted in adults. A total of 131 genes were differentially-regulated in pup brains following maternal exposure to MeHg, 50 of which were specific to MeHgCys and 35 specific to MeHgCl. Regulated genes were significantly enriched for several annotation categories including metal/zinc-binding and transcription regulation. In contrast few antioxidant genes were differentially regulated. This analysis provided insight into mechanisms by which MeHg may impair cellular processes in addition to behavioral impairments such as those associated with learning and memory. The results show differences between the toxic impacts of MeHg species, and also highlight the potential utility of an integrated approach incorporating gene expression with behavioral endpoints.
Key Words: toxicogenomics; seafood safety; methylmercury; zinc finger; neurobehaviour; teratogen.