| Adulthood: the definition of postnatal, young, adult, old animals is quite different among |
| scientists, also because of substantial lack of precise terms of comparison between different |
| species [29]; this point is important since postnatal/adult neurogenesis is heavily affected |
| by age; an attempt to equate the neurodevelopmental literature across species with |
| differences in gestation and maturation of various species has been reported [30]. |
| Identity of neural progenitors: progenitors are indicated as neuronal/glial either on the basis |
| of their nature (e.g., SVZ astrocytes are glial progenitors since they express GFAP) or |
| referring to their ultimate fate (e.g., SVZ astrocytes are neuronal progenitors since they lead |
| to the production of new neuroblast/neurons); parenchymal progenitors are even more |
| undefined both in their nature and fate [17, 31]. |
| Cell proliferation, cell genesis, and neurogenesis: many reports on adult neurogenesis |
| describe processes of cell proliferation without providing substantial proof on the outcome |
| of the proiliferative event; in the adult mammalian brain, complete neurogenesis occurs |
| only in the SVZ and SGZ neurogenic sites; this process is sustained by bona fide stem cells |
| harboured within stem cell niches which persist from primitive embryonic germinal layers |
| [9]; most neurogenesis in nonneurogenic regions, both in physiological and lesion-induced |
| conditions, seems to be incomplete, since newly born elements not only barely survive, but also |
| they do not functionally integrate, their ultimate fate remaining undiscovered [32]. |
| Protracted (postnatal) versus persistent (adult) neurogenesis: the end of developmental |
| neurogenesis is highly heterogeneous in the mammalian species concerning both |
| topographical and temporal variations within the same brain region; a distinction should be |
| done between “protracted” neurogenesis (a transitory extension of developmental |
| neurogenesis for some periods after birth) and “persistent” neurogenesis (namely, a |
| constitutive/physiological neurogenic process that can decrease in intensity but does not |
| cease during life time) [32–34]; protracted neurogenesis can involve both transient |
| germinal layers [35] and parenchymal neurogenesis [18]. |
| Conclusions driven from animal models: results obtained from some transgenic animal |
| models are highly controversial; in the text an example is given concerning the hypothetical |
| genesis of neurons from polydendrocytes in the piriform cortex; a discussion of this issue |
| can be found in [36]. |
| Conclusions driven from in vivo versus in vitro experiments: many in vitro conditions are able |
| to induce multipotency in progenitor cells which do not manifest the same differentiative |
| plasticity in vivo, especially within the CNS parenchyma [37, 38]. |
| Brain regeneration/repair: regeneration is a process which restores the interrupted |
| continuity of a missing organ mass, yielding new fully functional tissue; repair is an |
| adaptation to loss of normal tissue through its restoration by scarring; thus, regeneration |
| restores the normal structure and function of the organ, whereas repair does not [39]; a |
| further distinction can be made between physiological (maintenance) and pathological |
| (reparative) regenerative processes. |
| Relationship between adult neurogenesis and brain repair: the fact that adult neurogenesis |
| actually occurs in the CNS of all vertebrates challenges the view of a simple relationship |
| between maintenance of neurogenic regions in the adult CNS and regenerative capability |
| [40, 41]; indeed, not all vertebrates are capable of CNS regeneration, and the occurrence of |
| neurogenesis is not always associated with regeneration [41]. |
