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...

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Detalles Bibliográficos
Autores: Rodríguez-Vázquez, Lucía, Martí-Clúa, Joaquín|||0000-0002-6774-0092
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:288677
Acceso en línea:https://ddd.uab.cat/record/288677
https://dx.doi.org/urn:doi:10.1002/cne.25005
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario: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.