Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain

Since the early 1960s, in vivo observations have shown the generation of new neurons from dividing precursor cells. Nevertheless, these experiments suffered from skepticism, suggesting that the prevailing labeling method, which incorporates tagged thymidine analogs, such as [3H]-thymidine or bromodeoxyuridine (BrdU), may not be detecting a proliferative event, but could rather mark DNA repair in postmitotic neurons. Even today many scientists outside the field are still skeptical, because the question of specificity for thymidine labeling has not been sufficiently answered. This current paper aims at evaluating the arguments that are used by proponents and skeptics of this method by (i) presenting histological evidence of specificity of BrdU labeling for neural stem cell/progenitor activity in the adult brain; (ii) validating and comparing BrdU labeling with other histological methods; and (iii) combining BrdU and labeling methods for apoptosis to argue against DNA repair being a major contribution of BrdU-positive cells.