Limited Ethanol Exposure Selectively Alters the Proliferation of Precursor Cells in the Cerebral Cortex


  • Michael W. Miller

    Corresponding author
    1. Research Service, Veterans Affairs Medical Center; and the Departments of Psychiatry and Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa.
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  • This research was funded by the Department of Veterans Affairs and the national Institutes of Health (Grants AA06916, AA07568, and DE07734).

Reprint requests: Michael W. Miller, M.D., Department of Psychiatry–M.E.B., University of Iowa College of Medicine, Iowa City, IA 52242-1000.


The present in vivo study tests the hypothesis that limited (4-day) exposure to ethanol differentially affects the proliferation of cortical precursors in the two cortical germinal zones [the ventricular zone (VZ) and the subventricular zone (SZ)] and their descendants in the mature brain. The offspring of pregnant rats fed a liquid diet containing 6.7% (v/v) ethanol when prosencephalic stem cells [gestation day (G) 6–69], VZ cells (G12–G15), and SZ cells were proliferating (G18–G21) throughout much of gestation (G6–G21). In addition, the offspring of rats pair-fed a liquid control diet or fed chow were examined. The pregnant dams were administered with bromodeoxyuridine (BrdU) on either G15 or G21. The ratio of the number of cells that incorporated BrdU to the total number (the labeling index) was determined 1-hr postinjection (i.e., on G15 or G21) or on postnatal day 60. Ethanol treatment between G6 and G21 reduced the ratio of cells labeled by an injection of BrdU on G15 in the fetus and in the adult, and increased the ratio of cells labeled on G21. Regardless of when the injection was placed, ethanol treatment between G6 and G9 had no effect upon the ratio of BrdU-labeled cells in the fetus or mature cortex. Exposure from G12 to G15 decreased the number of VZ cells in the fetus and the number of immunolabeled cells in the adult cortex labeled by an injection on G15. This exposure had no effect on the incorporation by SZ cells. In contrast, ethanol exposure from G18 to G21 increased the labeling indices for fetal SZ cells and for cells in the adult, but it had no effect on the ratio of labeled VZ cells. Although ethanol had no apparent effect on the proliferation of stem cells, it did alter the proliferation of cells in the VZ and SZ. These effects are time-dependent and underlie the ethanol-induced changes in the number of cells in the adult.