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Keywords:

  • alcohol;
  • cerebral cortex;
  • cell cycle;
  • [3H]thymidine autoradiography

Abstract

Prenatal exposure to ethanol alters the generation of neocortical neurons; ethanol reduces the numbers of neurons generated between gestational day (G) 12 and G19 but paradoxically increases neuronogenesis after G19. The present study used [3H]thymidine autoradiography to examine the effects of ethanol on the proliferation of cells in the two cortical germinal zones, the ventricular and subventricular zones. Pregnant rats were fed one of three diets: a liquid ethanol-containing (6.7% v/v) diet (Et), a nutritionally matched isocaloric liquid diet (Ct), or chow and water (Ch). Fetuses were administered with [3H]thymidine on G13, G17, or G20 and killed 45–60 minutes later. Autoradiographs were prepared to identify radiolabeled and mitotic cells. Additional brains from 13–23-day-old fetuses were processed for cytoarchitectonic analyses.

The size of the lateral ventricles in the fetuses was not significantly affected by the prenatal exposure. Both the ventricular and subventricular zones were evident throughout the period from G13 to G23. In all three groups, the ventricular zone was thickest from G13 to G17, but from G15 on, the ventricular zone of Et-treated fetuses was significantly thinner than those of either controls. On G13, G17, and G20, the labeling index (the ratio of radiolabeled cells to the total population) was significantly less in Et-treated fetuses. The mitotic index was similar in Et-, Ch-, and Ct-treated fetuses. The subventricular zone of all fetuses was most prominent during later fetal ages and it was thicker in Et-treated fetuses than in controls. Moreover, the labeling and mitotic indices for the subventricular zone of Et-treated rats were significantly greater than for controls.

Thus, ethanol had different effects on the two neocortical germinal zones: the proliferation of ventricular cells was inhibited, whereas the proliferation of subventricular cells was stimulated. These data suggest that ethanol-induced changes in neuronogenesis result from alterations in proliferative activity.