Adult Neurogenesis 50 Years Later: Limits and Opportunities in Mammals

After five decades of research in adult neurogenesis (AN) it is far from easy to make a balance. If this field was a movie genre, brain repair goals would be a dreary mystery (with cell replacement therapies approaching fantasy), opportunities would be high quality science fiction, and limits could well belong to a hopeless thriller. Though apparently depicting a pessimistic screenplay, these aspects actually represent very exciting plots in which the only pitfall had been the attitude of those main characters (the scientists) who, starting with the re-discovery of AN (Paton and Nottebohm, 1984; Lois and Alvarez-Buylla, 1994), looked for neuronal cell replacement. The chimera of regenerative outcomes led to an exponential burst of studies: more than 7500 articles on PubMed with the keyword “adult neurogenesis.” Why such an interest many years after the first demonstration of AN (Altman andDas, 1965)?Maybe because the first isolation of neural stem cells (NSCs) took place in the same period (Reynolds andWeiss, 1992), thus making it possible to figure out continuous replenishment of new neurons throughout a brain’s life (Gage, 2000; Alvarez-Buylla et al., 2001). At the same time, the possibility to play in vitro with the NSC plasticity (Galli et al., 2003) might explain why the AN articles in PubMed become 23,000 when the keyword “neural stem cell” is employed.