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

Lucía Rodríguez‐Vázquez, Joaquín Martí

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1081-1096
Number of pages16
JournalJournal of Comparative Neurology
Volume529
Issue number5
DOIs
Publication statusPublished - 1 Apr 2021

Keywords

  • 5-bromo-2′-deoxyuridine
  • RRID: AB_10013660
  • RRID: AB_2313609
  • RRID: AB_258588
  • RRID: AB_476884
  • RRID: AB_628110
  • apoptosis
  • cerebellar neuroepithelium
  • embryonic life
  • immunohistochemistry
  • transmission electron microscopy
  • NEURAL STEM
  • 5-bromo-2 '-deoxyuridine
  • ORIGIN
  • BROMODEOXYURIDINE
  • DNA
  • 5-BROMODEOXYURIDINE
  • NEUROGENESIS
  • S-PHASE
  • SENESCENCE
  • CYCLE
  • IMMUNOHISTOCHEMISTRY

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