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Cerebral Cortex Advance Access published online on May 27, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh066
© 2004 by Oxford University Press
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Article

Ethanol Induces Heterotopias in Organotypic Cultures of Rat Cerebral Cortex

Sandra M. Mooney 1, Julie A. Siegenthaler 1, Michael W. Miller 2*

1 Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
2 Department of Neuroscience and Physiology, SUNY 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

Abnormalities in the migration of cortical neurons to ectopic sites can be caused by prenatal exposure to ethanol. In extreme cases, cells migrate past the pial surface and form suprapial heterotopias or ‘warts’. We used organotypic slice cultures from 17-day-old rat fetuses to examine structural and molecular changes that accompany wart formation. Cultures were exposed to ethanol (0, 200, 400 or 800 mg/dl) and maintained for 2-32 h. Fixed slices were sectioned and immunolabeled with antibodies directed against calretinin, reelin, nestin, GFAP, doublecortin, MAP-2 and NeuN. Ethanol promoted the widespread infiltration of the marginal zone (MZ) with neurons and the focal formation of warts. The appearance of warts is time- and concentration-dependent. Heterotopias comprised migrating neurons and were not detected in control slices. Warts were associated with breaches in the array of Cajal-Retzius cells and with translocation of reelin-immunoexpression from the MZ to the outer limit of the wart. Ethanol also altered the morphology of the radial glia. Thus, damage to the integrity of superficial cortex allows neurons to infiltrate the MZ, and if the pial-subpial glial barrier is also compromised these ectopic neurons can move beyond the normal cerebral limit to form a wart.

Key Words: alcohol, Cajal-Retzius cells, doublecortin, ectopia, fetal alcohol syndrome, migration, radial glia, reelin


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