Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: a tissue culture study.

To investigate whether ethanol has direct effects on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain with thymidine autoradiography. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants with [3H]thymidine, the explants were cultured for 48 h, and then distribution of labeled cells was evaluated autoradiographically. Adding 3.0 or 6.0 mg/ml ethanol to the culture medium caused significantly decreased distribution of labeled cells in the outer intermediate [control: 2.0+/-0.6% (mean+/-S.D.); 1.0 mg/ml ethanol: 2.1+/-1.5%; 3.0 mg/ml ethanol: 0. 5+/-1.5% (P<0.05); 6.0 mg/ml ethanol: 0.4+/-0.5% (P<0.05)] and the inner intermediate-A zones [control: 19.5+/-6.2%; 1.0 mg/ml ethanol: 13.1+/-8.6%; 3.0 mg/ml ethanol: 3.0+/-3.4% (P<0.01); 6.0 mg/ml ethanol: 5.2+/-2.9% (P<0.01)] compared to the control group. The mitotic index after 48-h culture was significantly reduced in the 6. 0 mg/ml ethanol group (0.260+/-0.114%; P<0.01) compared to the control group (0.600+/-0.158%). This suggests that ethanol inhibits neuronal migration in the cerebral cortex, although prolongation of the cell cycle by ethanol may contribute to the decreased number of labeled cells in the outer intermediate and inner intermediate-A zones. Furthermore, an abnormally dense and tortuous staining pattern of immunoreactive products of N-CAM was seen on the surface of migrating neurons in the 3.0 and 6.0 mg/ml ethanol groups, while the L1 staining pattern did not differ between the control and ethanol groups. These results suggest that abnormal expression of N-CAM may be involved in the inhibition of neuronal migration by ethanol.