Adult neurogenesis 20 years later: physiological function vs. brain repair.

Abstract

Two decades of intense investigation in the field of adult neurogenesis (AN) provided us with a fully renewed vision of brain plasticity, involving stem/progenitor cells capable of generating new neurons and glial cells throughout life. We know for sure that new neurons produced within canonical stem cell niches do play a significant role in cognitive tasks (learning/memory) operated by specific neural systems (Lepousez et al., 2013; Aimone et al., 2014). The fact that neural stem/progenitor cells (NSC) produce new elements that can integrate within some regions of the mature brain, replacing lost neurons/glial cells or adding to pre-existent neural circuits, appears extremely fascinating in the perspective of regenerative therapeutic approaches. Since the burst of investigations in AN/NSC field in the nineties, many neurobiologists addressed their studies on brain plasticity in the hope of brain repair, often discussing their results in a translational context. Nevertheless, in spite of striking efforts to clarify mechanisms/factors regulating AN and its physiological function, the question whether it can be exploited for healing neurologic diseases remains unsolved. More recent findings revealed additional examples of “non-canonical” neurogenesis and gliogenesis in various regions of the mammalian central nervous system (CNS; reviewed in Bonfanti and Peretto, 2011). These discoveries also open new hopes for brain repair, since the occurrence of spontaneous neuro-gliogenesis within the parenchyma does represent an endogenous source of progenitor cells even outside the restricted environment of canonical neurogenic sites. Nevertheless, parenchymal cell genesis remains substantially obscure as to its functional meaning(s) and outcome(s), and not yet exploitable for brain repair. Such an impasse largely resides on evolutionary discrepancies: most vertebrates use AN for brain repair as a byproduct of evolution, in addition to its physiological functions; mammals have lost such capacity, mainly because of unfavorable environments for repair/regeneration in their mature CNS (Bonfanti, 2011). A scarce perception of these facts might have produced misconceptions among scientists, sometimes leading to attitudes of unconditional optimism.