BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation
- PMID: 17020783
- DOI: 10.1016/j.brainresrev.2006.08.002
BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation
Abstract
Bromodeoxyuridine (BrdU) is a thymidine analog that incorporates DNA of dividing cells during the S-phase of the cell cycle. As such, BrdU is used for birth dating and monitoring cell proliferation. BrdU immunohistochemistry has been instrumental for the study of the development of the nervous system, and to confirm that neurogenesis occurs in the adult mammalian brain, including in human. However, the use of BrdU for studying neurogenesis is not without pitfalls and limitations. BrdU is a toxic and mutagenic substance. It triggers cell death, the formation of teratomas, alters DNA stability, lengthens the cell cycle, and has mitogenic, transcriptional and translational effects on cells that incorporate it. All of which have profound consequences on neurogenesis. BrdU is not a marker of the S-phase of the cell cycle. As a thymidine analog, it is a marker of DNA synthesis. Therefore, studying neurogenesis with BrdU requires distinguishing cell proliferation and neurogenesis from other events involving DNA synthesis, like DNA repair, abortive cell cycle reentry and gene duplication. BrdU labeling is currently the most used technique for studying adult neurogenesis in situ. However in many instances, appropriate controls have been overlooked and events reported as the generation of new neuronal cells in the adult brain misinterpreted, which makes BrdU labeling one of the most misused techniques in neuroscience.
Similar articles
-
Bromodeoxyuridine infused into the cerebral ventricle of adult mice labels nigral neurons under physiological conditions--a method to detect newborn nerve cells in regions with a low rate of neurogenesis.J Neurosci Methods. 2009 Nov 15;184(2):327-31. doi: 10.1016/j.jneumeth.2009.08.007. Epub 2009 Aug 20. J Neurosci Methods. 2009. PMID: 19699232
-
The evaluation of early embryonic neurogenesis after exposure to the genotoxic agent 5-bromo-2'-deoxyuridine in mice.Neurotoxicology. 2007 Jul;28(4):780-9. doi: 10.1016/j.neuro.2006.07.017. Epub 2006 Aug 1. Neurotoxicology. 2007. PMID: 16956662
-
BrdU assay for neurogenesis in rodents.Nat Protoc. 2006;1(3):1399-405. doi: 10.1038/nprot.2006.224. Nat Protoc. 2006. PMID: 17406427
-
Protocols for studying adult neurogenesis: insights and recent developments.Regen Med. 2007 Jan;2(1):51-62. doi: 10.2217/17460751.2.1.51. Regen Med. 2007. PMID: 17465775 Review.
-
Bromodeoxyuridine and the detection of neurogenesis.Curr Pharm Biotechnol. 2007 Jun;8(3):127-31. doi: 10.2174/138920107780906531. Curr Pharm Biotechnol. 2007. PMID: 17584085 Review.
Cited by
-
Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice.Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):E1045-54. doi: 10.1073/pnas.1219563110. Epub 2013 Feb 21. Proc Natl Acad Sci U S A. 2013. PMID: 23431204 Free PMC article.
-
Analysis of morphological changes as a key method in studying psychiatric animal models.Cell Tissue Res. 2013 Oct;354(1):41-50. doi: 10.1007/s00441-012-1547-9. Epub 2013 Jan 20. Cell Tissue Res. 2013. PMID: 23334194 Free PMC article. Review.
-
The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.Biomed Res Int. 2015;2015:126078. doi: 10.1155/2015/126078. Epub 2015 Feb 11. Biomed Res Int. 2015. PMID: 25759813 Free PMC article.
-
The C. elegans adult male germline: stem cells and sexual dimorphism.Dev Biol. 2010 Oct 15;346(2):204-14. doi: 10.1016/j.ydbio.2010.07.022. Epub 2010 Jul 24. Dev Biol. 2010. PMID: 20659446 Free PMC article.
-
Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy.J Neurosci. 2010 Jun 23;30(25):8613-23. doi: 10.1523/JNEUROSCI.5272-09.2010. J Neurosci. 2010. PMID: 20573907 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
