Frankel Samuel, Concannon John, Brusky Kristen, Pietrowicz Erik, Giorgianni Stephen, Thompson W Douglas, Currie Douglas A
Department of Biological Sciences and Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth Street, Portland, ME 04103, United States.
Neurotoxicology. 2009 Jul;30(4):529-37. doi: 10.1016/j.neuro.2009.02.015. Epub 2009 Mar 6.
Arsenic has neurotoxic effects on both central and peripheral components of the mature nervous system. There is increasing evidence that exposure to arsenic is also toxic to the developing nervous system and can result in decreased cell division and increased apoptosis in cultured developing neurons. However, the effects of arsenic on subsequent neuron growth and morphology remain unclear. In the present study we used differentiating PC12 cells to investigate the effects of sodium arsenite on the early stages of neurite production and growth. We find that arsenic has concentration- and time-dependent effects on initial neurite outgrowth in vitro. Exposure to low micromolar levels of sodium arsenite for five days results in reduced neurite production, outgrowth and complexity in newly differentiating PC12 cells. Furthermore, we find that exposure of more mature PC12 cells to arsenite can inhibit further neurite development. These results suggest that exposure to arsenic can disrupt early stages of neuron differentiation by altering the normal progression of morphological development and could potentially contribute to compromised long term functioning of neurons.
砷对成熟神经系统的中枢和外周部分均具有神经毒性作用。越来越多的证据表明，接触砷对发育中的神经系统也有毒性，可导致培养的发育中神经元的细胞分裂减少和细胞凋亡增加。然而，砷对后续神经元生长和形态的影响仍不清楚。在本研究中，我们使用分化的PC12细胞来研究亚砷酸钠对神经突产生和生长早期阶段的影响。我们发现砷在体外对初始神经突生长具有浓度和时间依赖性效应。将新分化的PC12细胞暴露于低微摩尔水平的亚砷酸钠五天会导致神经突产生、生长和复杂性降低。此外，我们发现将更成熟的PC12细胞暴露于亚砷酸盐可抑制神经突的进一步发育。这些结果表明，接触砷可通过改变形态发育的正常进程来破坏神经元分化的早期阶段，并可能导致神经元长期功能受损。
