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Cerebral Cortex Advance Access published online on April 14, 2004

Cerebral Cortex, doi:10.1093/cercor/bhh039
© 2004 by Oxford University Press
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Article

Transforming Growth Factor {beta}1 Modulates Cell Migration in Rat Cortex: Effects of Ethanol

Julie A. Siegenthaler 1 Michael W. Miller 2*

1 Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA
2 Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, NY 13210, USA; Research Service, Veterans Affairs Medical Center, Syracuse, NY 13210, USA

* To whom correspondence should be addressed. E-mail: millermw{at}upstate.edu.


   Abstract

Transforming growth factor (TGF) {beta}1 regulates cell migration of non-neural cells. Hence, two hypotheses were tested: (i) that TGF{beta}1 affects cell migration and the expression of associated adhesion proteins in developing cortex; and (ii) that these effects are antagonized by ethanol. The effects of TGF{beta}1 (2.5-40 ng/ml) and ethanol (400 mg/dl) on cell migration were examined in organotypic cultures from fetal rat brains. Migration was determined by tracing the movement of cells pulse-labeled with bromodeoxyuridine. Cell migration was altered by TGF{beta}1 in a concentration-dependent manner: at low concentrations, cell migration was promoted whereas at high concentrations TGF{beta}1 impeded migration. Ethanol treatment alone reduced the rate of migration. Interestingly, the rate of cell migration in slices treated with both TGF{beta}1 and ethanol was the same as that in untreated cultures. The expression of cell adhesion proteins (nCAM, integrin {alpha}3, {alpha}v and {beta}1) was differentially effected by TGF{beta}1 and/or ethanol. TGF{beta}1 increased the expression of these adhesion proteins in a progressive, concentration-dependent manner. Likewise, ethanol also increased adhesion protein expression, however, combined TGF{beta}1 and ethanol treatment reduced expression. Collectively, the data show that TGF{beta}1 alters cell migration in the developing cortex and that the TGF{beta}1 system is a target of ethanol toxicity.

Key Words: alcohol, fetal alcohol syndrome, integrin, nCAM, parietal cortex, somatosensory cortex, TGF{beta}1


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