ToxSci Advance Access published online on May 22, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp105
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Methylmercury speciation influences brain gene expression and behaviour in gestationally-exposed mice pups
* National Institute of Nutrition and Seafood Research, Postboks 2029 Nordnes, 5817 Bergen, Norway (aha{at}nifes.no; sja{at}nifes.no)
School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand (chris.glover@canterbury.ac.nz)
Nutritional Sciences Division, School of Biomedical and Health Sciences, King's College London, SE1 9NH, U.K. (christer.hogstrand{at}kcl.ac.uk; dzheng{at}sgul.ac.uk)
Anatomy and Human Sciences, School of Biomedical and Health Sciences, King's College London, SE1 9NH, U.K. (gillian.sales{at}kcl.ac.uk)
Corresponding author: Chris Glover, Biology Building, School of Biological Sciences, University of Canterbury, Ilam, Christchurch 8140, New Zealand, Ph: +64 3 364 4097, Fax: +64 3 364 2590, e-mail: chris.glover{at}canterbury.ac.nz
Received March 27, 2009; revision received May 14, 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–1, for eleven weeks (inclusive of three weeks gestational and two 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 neurobehavioural endpoints. There were no differences in tissue Hg accumulation between the two forms of MeHg presented, but differences in pup behaviour 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 behavioural 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 behavioural endpoints.
Key Words: toxicogenomics; seafood safety; methylmercury; zinc finger; neurobehaviour; teratogen.