Adult Neurogenesis 50 Years Later: Limits and Opportunities in Mammals

Afterfivedecadesofresearchinadultneurogenesis(AN)itisfarfromeasytomakeabalance.If thisfieldwasamoviegenre,brainrepairgoalswouldbeadrearymystery(withcellreplacement therapiesapproachingfantasy),opportunitieswouldbehighqualitysciencefiction,andlimits could wellbelongtoahopelessthriller.Thoughapparentlydepictingapessimisticscreenplay, theseaspectsactuallyrepresentveryexcitingplotsinwhichtheonlypitfallhadbeentheattitude of thosemaincharacters(thescientists)who,startingwiththere-discoveryofAN(Patonand Nottebohm,1984;LoisandAlvarez-Buylla,1994), lookedforneuronalcellreplacement.The chimera ofregenerativeoutcomesledtoanexponentialburstofstudies:morethan7500articles on PubMedwiththekeyword“adultneurogenesis.”Whysuchaninterestmanyyearsafterthefirst demonstration ofAN(Altman andDas,1965)?Maybebecausethefirstisolationofneuralstemcells (NSCs) tookplaceinthesameperiod(ReynoldsandWeiss,1992), thusmakingitpossibletofigure out continuousreplenishmentofnewneuronsthroughoutabrain’slife(Gage,2000;Alvarez-Buylla et al.,2001). Atthesametime,thepossibilitytoplay in vitro withtheNSCplasticity(Gallietal., 2003) mightexplainwhytheANarticlesinPubMedbecome23,000whenthe keyword“neural stem cell”isemployed.