Do large brains of long-living mammals prefer non-newly generated, immature neurons?

Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases, dementia and other age-related problems affecting the central nervous system (CNS) do represent a heavy health and social burden. Efficacious regenerative processes are not a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced (if compared to those occurring in non-mammalian vertebrates) and hardly inducible by therapeutic approaches (reviewed in Martino et al., 2011). Paradoxically, different types of remarkable structural plastic processes have been shown to occur in the young and adult mammalian brain, spanning from widespread synaptic plasticity and gliogenesis to a more spatially-restricted, yet clearly demonstrable, genesis of new neurons (references in Martino et al., 2011). The failure in mammalian brain regeneration can be explained by a combination of several factors acquired through evolution (e.g., brain complexity, scarcity of stem cells, incapability of cell de-differentiation, role of immune system; see Bonfanti, 2011 for review). Ultimately, all aspects involved converge into two main reasons: i) unlike non-mammalian vertebrates (e.g., fish or amphibians) in which neurogenic processes are far more extended and also provide repair, mammals have retained mostly the physiological role of plasticity, useful to cope with environmental changes but hardly helpful in regeneration; ii) adult mammalian neurogenesis appears to be highly reduced in humans with respect to rodents (Sanai et al., 2011; Paredes et al., 2015), recent work carried out in dolphins further confirming that it can be vestigial in large-brained, long-living mammals (Parolisi et al., 2017). Especially humans face further neurological risks in the future since they possess less potential for brain regeneration than other animal species in contrast with their extended (and progressively increasing) lifespan.