Cadmium modulates proliferation and differentiation of human neuroblasts.

Cadmium is an environmental pollutant inducing numerous pathological effects, including neurological disorders and brain diseases. However, little is known about the molecular mechanisms of cadmium in affecting neurons and in inducing neurotoxicity in the development of the human brain. We have recently established, cloned, and propagated in vitro a primary long-term cell culture (FNC-B4) obtained from the human fetal olfactory neuroepithelium. In the present study, we show that different concentrations of cadmium chloride (CdCl(2)) induced dose-dependent biological effects in FNC-B4 cells. A low concentration (10 microM) of CdCl(2) stimulated neuroblast growth, whereas a high concentration (100 microM) inhibited the growth and the viability of neuroblasts inducing morphological and cytoskeletal alterations as well as apoptotic cell death. We also observed that CdCl(2) affected, in a dose-dependent manner, the differentiation of FNC-B4 neuroblasts, with increased mRNA and protein levels of differentiation markers and decreased expression levels of neuronal stem markers. Furthermore, differentiated cells co-expressed glial and neuronal markers. We suggest that CdCl(2) in FNC-B4 neuroblasts might represent a selective cue by which, in a heterogeneous primary culture, the more differentiated mature cells die, whereas the undifferentiated cells, at the same time glial and neuronal progenitors, are forced to access a state of differentiation. 2008 Wiley-Liss, Inc.