Siegenthaler Julie A, Miller Michael W
Department of Neuroscience and Physiology, State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.
J Neurochem. 2005 Nov;95(3):902-12. doi: 10.1111/j.1471-4159.2005.03461.x. Epub 2005 Sep 29.
Ethanol is a potent teratogenic agent that disrupts several aspects of neuronogenesis, including the proliferation rate of cortical precursors. With regard to corticogenesis, possible targets of ethanol toxicity include soluble factors, like transforming growth factor beta1 (TGFbeta1), that regulate cortical growth and cell cycle proteins that control the kinetics of the cell cycle. The effect of ethanol on normal cell proliferation and TGFbeta1-regulated cell proliferation in the developing cortex was assessed using an organotypic slice culture model. Ethanol elongated the cell cycle, possibly through a decrease in the expression of G1 cell cycle protein cyclin D1. Further, ethanol exposure antagonized the anti-proliferative action of TGFbeta1 and blocked TGFbeta1-dependent increases in cell cycle inhibitor p21. Collectively, this evidence suggests that disruption of appropriate cell cycle protein expression and inhibition of TGFbeta1 activity are potential mechanisms underlying the effect of ethanol on cortical development.
