Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits

Katie Sokolowski, Maryann Obiorah, Kelsey Robinson, Elizabeth Mccandlish, Brian Buckley, Emanuel Dicicco-Bloom

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)936-949
Number of pages14
JournalDevelopmental Neurobiology
Volume73
Issue number12
DOIs
StatePublished - Dec 2013

All Science Journal Classification (ASJC) codes

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Keywords

  • Apoptosis
  • Development
  • Hippocampus
  • Methylmercury
  • Neural stem cell

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