Role of brominated diphenyl ether-209 in the proliferation and apoptosis of rat cultured neural stem cells in vitro

The congener brominated diphenyl ether 209 (BDE-209) is a high-bromine polybrominated di-phenyl ether (PBDE) and a common flame retardant that is applied to electronic equipment. In this study, we investigated the effects of BDE209 on the regulation of proliferation and apoptosis of neural stem cells (NSCs) and determined the underlying protein alterations. We cultured NSCs and exposed them to different BDE-209 concentrations to assess the effects of BDE209 on cell proliferation. Flow cytometric assays were used to assess the effects of BDE209 on apoptosis and to determine the underlying mechanisms. The expression levels of nuclear factor kappa B (NF-kappa B), apoptotic-associated protein cleaved caspase-3 and caspase-3, phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) were analyzed by western blot assays. Our data indicated that BDE-209 decreased NSC proliferation in a concentration-dependent manner. BDE-209 induced the activation of NF-kappa B; however, the expression levels of phosphorylated JNK1/2 (p-JNK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were not altered. Furthermore, BDE209 increased apoptosis and protein levels of cleaved caspase 3, whereas the NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC) attenuated BDE-209-induced apoptosis. In conclusion, BDE209 inhibits NSC proliferation in vitro, and BDE209 is able to induce apoptosis, which may be associated with the activation of NF-kappa B pathways.