Adult neurogenesis twenty years later: physiological function versus brain repair

Two decades of huge investigation in adult neurogenesis (AN) provided us with an utterly new vision of brain plasticity, involving stem/progenitor cells capable of generating new neurons and glial cells throughout life. Most neurobiologists addressed this biological process in the perspective of brain repair. Nevertheless, in spite of striking efforts, the question whether AN can be exploited for healing neurologic diseases remains unsolved. Such an impasse is mainly due to the fact that most vertebrates produce brain repair using AN as a byproduct of evolution in addition to its physiological function, whereas mammals do not. Among scientists, a scarce perception of this fact might have produced misinterpretations. Our knowledge in mammals allows to fix four main statements: i) two neurogenic zones harbouring stem cell niches provide neural cell renewal in certain systems (olfactory bulb and hippocampus); ii) wide areas of the nervous system host many parenchymal progenitors, which appear to be quite heterogeneous and obscure in nature, outcome, and function; iii) both neurogenic zones and parenchymal progenitors are activated in different physiological/pathological conditions; iv) in spite of such activation, the response to pathological conditions is generally non-coordinated and/or abortive, not leading to brain repair.
This topic is intended to address the relationships between existence of neural stem/progenitor cells (playing homeostatic roles in AN and responding to pathological conditions) and lack of effective reparative outcome in terms of regenerative neurology. Contributions are expected to focus on the possible aspects which affect such discrepancy/interplay in different contexts. Critical discussion and new theories/hypothesis are solicited, from both pro-reparative and skeptical schools. Opinion papers and commentaries will be preferentially considered, in order to picture future landscapes for the AN field in the perspective of restorative medicine.

Specific points to be addressed:

- Are AN physiological function(s) and its possible role in brain repair two separate domains in mammals?

- Can comparative analyses elucidate the interplay between AN physiological role(s)
and species-specific repair/regenerative capabilities ?

- To which extent brain regenerative capability is a byproduct of evolution?

- To which extent the knowledge of mechanisms in physiological AN can implement brain repair?

- To which extent tissue environment can determine the outcome of AN? (e.g., mammals versus non mammalian species, neurogenic niches versus parenchyma)

- AN and repair in humans versus animal models

- Does cell mobilization from neurogenic niches towards adjacent injuries really play a role in repair?

- Can AN be complementary to plasticity of pre-existent elements? (e.g. in rehabilitation)

- Quiescent versus active parenchymal progenitors: where we are and what is needed. How parenchymal progenitors can be induced in a repair perspective?

- Which is the ultimate impact of AN in the whole brain function?

- Can pitfalls in methodological approaches affect the results of AN studies? Do we need adjustments in the peer review process of AN manuscripts to deal with gaps in experimental plan and result interpretation?

- Bystander effect(s) versus cell replacement