In Vitro Cytotoxic Effects of Tin Compounds on Normal Human Astrocytes

摘要

Astrocyte proliferation is strictly controlled both during development and in the adult nervous system. Stannous chloride (SnCL,) an inorganic tin, stimulated the nervous system when injected into laboratory animals. It also induced extensive DNA damage. In the present study, we investigated the effects of SnCl_2 and stannous 2-ethylhexanoate [Sn(Oct)2] at different concentrations on the proliferation and development of normal human astrocytes (NHA). Cells were cultured with SnCl_2 or Sn(Oct)2, and the number of viable cells and the presence of neural cell-specific genes were determined to assess their proliferation, gap-junctional intercellular communication (GJIC) function, and development, respectively. Cell proliferation, GJIC function, and theexpression of gap junctional proteins were suppressed when NAH were cultured with SnCL, and Sn(Oct)2. It was reported that the proliferating cells initially express nestin, a gene specific for neural precursor cell which subsequently give rise to neurons, oligodendrocytes, and astrocytes. Here, we examined the expression of neural cell-specific genes using real-time polymerase chain reaction (PCR). Expression of genes specific for neural precursor cells and astrocytes was decreased, while expression ofgenes specific for neurons and oligodendrocytes was increased with Sn(Oct)2, but all were decreased with SnCl_2 compared with the control culture. Our findings suggest that these tin compounds are neurotoxic to astrocytes, resulting in the suppression ofthe proliferation and development of NHA.