5-Bromo-2’-deoxyuridine labeling: historical perspectives, factors influencing the detection, toxicity, and its implications in the neurogenesis

The halopyrimidine 5-bromo-2′-deoxyuridine (BrdU) is an exogenous marker of DNA synthesis. Since the introduction of monoclonal antibodies against BrdU, an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA. BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic, perinatal, and adult neurogenesis in a variety of vertebrate species including birds, reptiles, and mammals. Due to BrdU toxicity, its incorporation into replicating DNA presents adverse consequences on the generation, survival, and settled patterns of cells. This may lead to false results and misinterpretation in the identification of proliferative neuroblasts. In this review, I will indicate the detrimental effects of this nucleoside during the development of the central nervous system, as well as the reliability of BrdU labeling to detect proliferating neuroblasts. Moreover, it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal, perinatal, and adult neurogenesis. Human adult neurogenesis will also be discussed. It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.