BrdU immunohistochemistry for studying adult neurogenesis: Paradigms, pitfalls, limitations, and validation

  title={BrdU immunohistochemistry for studying adult neurogenesis: Paradigms, pitfalls, limitations, and validation},
  author={Philippe Taupin},
  journal={Brain Research Reviews},
  • P. Taupin
  • Published 31 January 2007
  • Biology
  • Brain Research Reviews
Application of BrdU in studying postnatal neurogenesis
In the developing rat brain, BrdU labeling showed regional distribution that was dose-, age- and survival time-dependent and provided useful information on Brd U application in the study of postnatal neurogenesis.
The dark side of BrdU in neural stem cell biology: detrimental effects on cell cycle, differentiation and survival
The results reveal so far uncharacterized effects of BrdU on adult NPCs, and it is concluded that, because of its ubiquitous use in stem cell biology, any potential effect ofBrdU of NPCs has to be scrutinized prior to interpretation of data.
Bromodeoxyuridine Induces Senescence in Neural Stem and Progenitor Cells
It is concluded that BrdU treatment induces a senescence pathway that causes a progressive decline in the replication of rapidly dividing stem/progenitor cells, suggesting a novel and uncharacterized effect of Brd U.
Neural stem cells exposed to BrdU lose their global DNA methylation and undergo astrocytic differentiation
It is shown that NSC grown in self-renewing conditions in vitro, when exposed to BrdU, lose the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial differentiation, strongly up-regulating the astrocytic marker GFAP.
The Cell Birth Marker BrdU Does Not Affect Recruitment of Subsequent Cell Divisions in the Adult Avian Brain
The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment in the brain.
Genetic Detection of Neurogenesis and Astrocytic Transformation of Radial Glia
The adult mammalian brain was long believed to be incapable of generating new neurons after the developmental stage. It is now known that specialized stem cell niches produce neurons throughout life
Flow cytometric analysis of BrdU incorporation as a high-throughput method for measuring adult neurogenesis in the mouse.
Synthetic Thymidine Analog Labeling without Misconceptions
The results indicate the potential caveats in labeling the replicating DNA using thymidine analogs and suggest guidelines for applying this approach and show that, in a wide range of doses, EdU and BrdU label similar numbers of cells in the dentate gyrus shortly after administration.
Bromodeoxyuridine inhibits cancer cell proliferation in vitro and in vivo.
The results suggest that BrdU may have an important role as an adjunctive therapeutic for a wide variety of cancers based on new insights into its effect as a negative regulator of cell cycle progression.


The cell cycle–apoptosis connection revisited in the adult brain
Evidence is presented that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of Brd U is directly infused into the brain.
Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat
Bromodeoxyuridine is a useful tool to study neural development, but its cytotoxicity represents a serious pitfall particularly when multiple doses are used to label cells.
Hypoxia-Ischemia Induces DNA Synthesis without Cell Proliferation in Dying Neurons in Adult Rodent Brain
The combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers and the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers.
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
A high dose of BrdU (300 mg/kg) is shown to be a specific, quantitative, and nontoxic marker of dividing cells in the adult rat dentate gyrus, whereas lower doses label only a fraction of the S‐phase cells.
Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population
Mathematically analysis, using one and two population models, indicates that over 90% of the proliferating cells in the dentate hilus at this age comprise a single population at least in terms of the lengths of the cell cycle and the S-phase.