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Administration of 5‐bromo‐2′‐deoxyuridine interferes with neuroblast proliferation and promotes apoptotic cell death in the rat cerebellar neuroepithelium
Author(s) -
RodríguezVázquez Lucía,
Martí Joaquín
Publication year - 2021
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.25005
Subject(s) - tunel assay , bromodeoxyuridine , biology , terminal deoxynucleotidyl transferase , apoptosis , neuroepithelial cell , proliferating cell nuclear antigen , immunohistochemistry , microbiology and biotechnology , neuroblast , deoxyuridine , programmed cell death , andrology , endocrinology , medicine , neurogenesis , embryonic stem cell , immunology , biochemistry , dna , gene
Abstract 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 μg/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 μg/g b.w. of BrdU. The reduction was more evident using 200 μg/g b.w. The most severe effects were found with 300 μg/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 μg/g b.w. of BrdU. The number of dying cells increased with 200 μg/g b.w. The most important number of apoptotic cells were observed in animals injected with 300 μg/g b.w. of BrdU. Ultrastructural studies confirmed the presence of neuroblasts at different stages of apoptosis.