Granule cell apoptosis induced by overdose copper and ethanol is counterbalanced by co-induced cellular proliferation in rat dentate gyrus

Abstract

Copper (Cu) is an essential element for life, however, is toxic at excessive doses, whereas exposure to ethanol (EtOH) has been known to cause morphological changes, degeneration and neuronal loss in central nervous system (CNS). In this study, the effect of overdose co-exposure to Cu and EtOH on dentate gyrus was investigated in rats. Analysis of apoptotic cell death on the basis of TdT-mediated dUTP nick end labeling (TUNEL) assay revealed that the rate of apoptosis was increased by 1.84 folds in treated group in comparison to that in controls (p < 0.0001). Analysis of cell proliferation on the basis of 5-bromo-2'-deoxy-uridine labeling assay, on the other hand, revealed a 1.49 fold increase in treated group when compared to controls (p < 0.006). Total number of granule cells in dentate gyrus of each group was estimated using the optical fractionator method. The results showed that mean granule cell number in dentate gyrus was 4.64% lower in treated group than that in control group, but this difference was not statistically significant (p > 0.05). These results suggest that the apoptotic effect of overdose Cu and EtOH on granule cells of dentate gyrus may be counterbalanced by the co-induced cellular proliferation, thereby maintaining the total granule cell number unaltered. © 2005 Tohoku University Medical Press.