Neurogenesis is Toxicologically Heterogeneous: A Case of BrdU-lnduced Cell Death

Summary

In developmental neuroscience, 5-bromo-2′-deoxyuridine (BrdU) is extensively used as a useful tool for labeling proliferating cells. Doses ranging from 10 to 100 mg/kg are commonly injected into animals. However, several lines of evidence demonstrated that BrdU has genotoxicity. The present study demonstrates that 1) a single injection of BrdU at 100 mg/kg into pregnant mice on gestation day 11.5 induced cell death in the neuroepithelium of certain brain areas such as the frontal neocortex, but not other areas such as the mesencephalic tegmentum and pons, 2) injections of BrdU into adult mice at 100 or 300 mg/kg did not induce cell death in the subventricular zone (SVZ) of the lateral ventricle, known to be a site of adult neurogenesis. These findings strongly suggest that 1) sensitivity to the genotoxicity differes among fetal neural stem cells, 2) BrdU-labeling should be avoided when early neurogenesis is being observed.