Premium
High susceptibility of neural stem cells to methylmercury toxicity: effects on cell survival and neuronal differentiation
Author(s) -
Tamm Christoffer,
Duckworth Joshua,
Hermanson Ola,
Ceccatelli Sandra
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03718.x
Subject(s) - neural stem cell , embryonic stem cell , methylmercury , biology , neurotoxicity , apoptosis , cellular differentiation , programmed cell death , neuroscience , calpain , stem cell , microbiology and biotechnology , transplantation , neural development , population , chemistry , toxicity , biochemistry , medicine , enzyme , ecology , bioaccumulation , organic chemistry , environmental health , gene
Neural stem cells (NSCs) play an essential role in both the developing embryonic nervous system through to adulthood where the capacity for self‐renewal may be important for normal function of the CNS, such as in learning, memory and response to injury. There has been much excitement about the possibility of transplantation of NSCs to replace damaged or lost neurones, or by recruitment of endogenous precursors. However, before the full potential of NSCs can be realized, it is essential to understand the physiological pathways that control their proliferation and differentiation, as well as the influence of extrinsic factors on these processes. In the present study we used the NSC line C17.2 and primary embryonic cortical NSCs (cNSCs) to investigate the effects of the environmental contaminant methylmercury (MeHg) on survival and differentiation of NSCs. The results show that NSCs, in particular cNSCs, are highly sensitive to MeHg. MeHg induced apoptosis in both models via Bax activation, cytochrome c translocation, and caspase and calpain activation. Remarkably, exposure to MeHg at concentrations comparable to the current developmental exposure (via cord blood) of the general population in many countries inhibited spontaneous neuronal differentiation of NSCs. Our studies also identified the intracellular pathway leading to MeHg‐induced apoptosis, and indicate that NSCs are more sensitive than differentiated neurones or glia to MeHg‐induced cytotoxicity. The observed effects of MeHg on NSC differentiation offer new perspectives for evaluating the biological significance of MeHg exposure at low levels.