title: Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits.
abstract: The developing brain is particularly sensitive to exposures to environmental contaminants. In contrast to the adult, the developing brain contains large numbers of dividing neuronal precursors, suggesting that they may be vulnerable targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature neurons in the CA1-3 region as well as neural stem cells (NSC) in the dentate gyrus (DG) hilus, which actively produce new neurons that migrate to the granule cell layer (GCL). Using this well-characterized NSC population, we examined the impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and subsequent adolescent learning and memory behavior. Assessing a range of exposures, we found that a single subcutaneous injection of 0.6 µg/g MeHg in P7 rats induced caspase activation in proliferating NSC of the hilus and GCL. This acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the hilus by 22% and the GCL by 27%, as well as reductions in neural precursor proliferation by 25%. In contrast, non-proliferative CA1-3 pyramidal neuron cell number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an adolescent spatial memory deficit as assessed by Morris water maze. These results suggest that environmentally relevant levels of MeHg exposure may decrease NSC populations and, despite ongoing neurogenesis, the brain may not restore the hippocampal cell deficits, which may contribute to hippocampal-dependent memory deficits during adolescence.
authors: Joint Graduate Program in Toxicology, Rutgers, The State University of New Jersey/Rutgers Graduate School of Biomedical Sciences, Piscataway, New Jersey; Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey.
authors: Katie
authors: K
authors: Sokolowski
authors: Maryann
authors: M
authors: Obiorah
authors: Kelsey
authors: K
authors: Robinson
authors: Elizabeth
authors: E
authors: McCandlish
authors: Brian
authors: B
authors: Buckley
authors: Emanuel
authors: E
authors: DiCicco-Bloom
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008569:Memory Disorders / Q000139:chemically induced*; D008767:Methylmercury Compounds / Q000633:toxicity*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008767:Methylmercury Compounds; C073972:dimethyl mercury
keywords: apoptosis; development; hippocampus; methylmercury; neural stem cell
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