Administration of 5-bromo-2′-deoxyuridine interferes with neuroblast proliferation and promotes apoptotic cell death in the rat cerebellar neuroepithelium

The current study was conducted to assess whether a single administration of 5-bromo-2'-deoxyuridine (BrdU) interferes with cell proliferation and leads to the activation of apoptotic cellular events in the prenatal cerebellum. BrdU effects across a wide range of doses (25-300 mu g/g b.w.) were analyzed using immunohistochemical and ultrastructural procedures. The pregnant rats were injected with BrdU at embryonic day 13, and their fetuses were sacrificed from 5 to 35 hr after exposure. The quantification of several parameters such as the density of mitotic figures, and BrdU and proliferating cell nuclear antigen (PCNA)-reactive cells showed that, in comparison with the saline injected rats, the administration of BrdU impairs the proliferative behavior of neuroepithelial cells. The above-mentioned parameters were significantly reduced in rats injected with 100 mu g/g b.w. of BrdU. The reduction was more evident using 200 mu g/g b.w. The most severe effects were found with 300 mu g/g b.w. of BrdU. The present findings also revealed that high doses of BrdU lead to the activation of apoptotic cellular events as evidenced by both terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and immunohistochemistry for active caspase-3. In comparison with saline rats, many apoptotic cells were found in rats injected with 100 mu g/g b.w. of BrdU. The number of dying cells increased with 200 mu g/g b.w. The most important number of apoptotic cells were observed in animals injected with 300 mu g/g b.w. of BrdU. Ultrastructural studies confirmed the presence of neuroblasts at different stages of apoptosis.

Automated summary

This study evaluated the effects of a single administration of BrdU on cell proliferation and apoptotic events in the prenatal cerebellum. Results showed that BrdU at various doses reduced mitotic figures and proliferating cells, with the most severe effects seen at higher doses. High doses of BrdU also led to the activation of apoptotic events, as shown by TUNEL assay and caspase-3 immunohistochemistry.