Methylmercury speciation influences brain gene expression and behavior in gestationally-exposed mice pups.
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.
Glover
Chris N
CN
National Institute of Nutrition and Seafood Research, 5817 Bergen, Norway. chris.glover@canterbury.ac.nz
Zheng
Dongling
D
Jayashankar
Shalini
S
Sales
Gillian D
GD
Hogstrand
Christer
C
Lundebye
Anne-Katrine
AK
D000375:Aging; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001822:Body Burden; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D004032:Diet; D005260:Female; D005506:Food Contamination; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D039382:Maternal Nutritional Physiological Phenomena; D020262:Mercury Poisoning, Nervous System / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
D008767:Methylmercury Compounds; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; C030589:methylmercury cysteine; D003545:Cysteine; C004925:methylmercuric chloride