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Nevertheless, as Spalding and colleagues point out, there are plenty of tissue banks with archived material which will always be useful.—Tom Fagan About 40 years ago, Joseph Altman and his colleagues used the 3H-thymidine autoradiographic method to birthdate cells in the brains of adult rats and cats, and reported evidence for neurogenesis in the olfactory bulb, hippocampus, and neocortex (1-5).These findings were corroborated and extended by Michael Kaplan and his colleagues by combining 3H-thymidine autoradiography with electron microscopy (16-19).However, others have not corroborated these findings (20,22,23), or have found evidence for adult neurogenesis only under conditions of damage (21,25,31).Methodological flaws have been proposed as explanations for putative false positive and false negative data on this subject (13,26).Despite this rather large body of work, the findings were not well-received by the neuroscience community, and adult neurogenesis in the mammalian brain remained a matter of debate (17,27, 28).In the late 1990s, the use of a newer technique, bromodeoxyuridine (Brd U) labeling, in combination with confocal microscopy, led to new evidence in support of this phenomenon and the acceptance of adult neurogenesis in the olfactory bulb and the hippocampus (11,13,14,24).This method was designed with the following facts in mind: 1) Levels of atmospheric C14 were very high during the time of intensive nuclear weapons testing (in the mid 1950s to early 1960s); and 2) carbon atoms in the DNA of cells do not turn over.
In today’s Cell, Frisen and colleagues report how they used the dating method to dismiss the possibility that neurogenesis takes place in the adult human cortex.
The development and application of new methods is clearly needed to resolve the debate about adult neurogenesis in neocortex and other “non-neurogenic” brain regions.
The recent publication in Cell by Spalding and colleagues (29) reported the use of a novel and highly innovative method to search for adult neurogenesis in human postmortem brain tissue.
As Paola Arlotta and Jeffrey Macklis from the Harvard Medical School write in an accompanying Cell perspective, historically, methods to label newborn cells, such as the use of tritium, bromodeoxyuridine (Brd U), or other halogenated urides, are toxic and cannot be used in humans, so the strategy developed by Spalding and colleagues “enables a more direct understanding of cell turnover, aging, and lifespan throughout the human body and those of other long-lived animals.” There is one small caveat, however.
Because atmospheric C14 levels are falling relatively quickly, the method will decrease in sensitivity with time, so the period during which it will be useful is limited and people born around the time of the nuclear tests will remain the most suited for study.
The authors suggest that previous reports of adult cortical neurogenesis might be technical artifacts.