Effects of low level of methylmercury on proliferation of cortical progenitor cells

Methylmercury (MeHg) is a potent environmental neurotoxin that shows toxicity to developing central nervous system (CNS), causing brain damage in children even at low exposure levels. However, the mechanisms for its effect on CNS are not well understood. In current study, primary cultures of progenitor cells from embryonic cerebral cortex were used as a model system to study the potential effect and the underlying mechanism of MeHg on neural progenitor cells. Results showed that, in cultured cortical progenitor cells, 48-h exposure to low-level of MeHg (at 2.5 nM, 5 nM and 50 nM, respectively) caused G1/S cell cycle arrest in a dose-dependent manner without inducing cell death. Interestingly, the expression of cyclin E, which promotes G1/S transition, but not cyclin D1 and CDK2, was selectively downregulated by exposure of MeHg. In addition, low-level of MeHg inhibited the maintenance of ERK1/2 phosphorylation, possibly by abolishing the late phase ERK1/2 activation induced by bFGF. Thus, MeHg may induce proliferation inhibition and cell cycle arrest of neural progenitor cells via regulating cyclin E expression and perturbing a pathway that involves ERK1/2.

Research Highlights
► Primary cultures of cortical progenitor cells was used as a model system to study the effect and the mechanism of MeHg neurotoxicity.
► Proliferation proliferation of neural progenitor cells is reduced by MeHg chronic exposure at nanomolar concentrations.
► Low levels of MeHg induced proliferation inhibition and cell cycle arrest is mediated via regulating cyclin E expression and perturbing a pathway that involves ERK1/2.