During the last two decades basic research in neuroscience has remarkably expanded due to the discovery of neural stem cells (NSCs) and adult neurogenesis in the mammalian central nervous system (CNS). The existence of such unexpected plasticity triggered hopes for alternative approaches to brain repair, yet deeper investigation showed that constitutive mammalian neurogenesis is restricted to two small “neurogenic sites” hosting NSCs as remnants of embryonic germinal layers and subserving homeostatic roles in specific neural systems. The fact that in other classes of vertebrates adult neurogenesis is widespread in the CNS and useful for brain repair sometimes creates misunderstandings about the real reparative potential in mammals. Nevertheless, in the mammalian CNS parenchyma, which is commonly considered as “nonneurogenic,” some processes of gliogenesis and, to a lesser extent, neurogenesis also occur. This “parenchymal” cell genesis is highly heterogeneous as to the position, identity, and fate of the progenitors. In addition, even the regional outcomes are different. In this paper the heterogeneity of mammalian parenchymal neurogliogenesis will be addressed, also discussing the most common pitfalls and misunderstandings of this growing and promising research field. 1. Introduction The discovery of neural stem cells (NSCs) at the beginning of the nineties led many people to consider definitively broken the dogma of the central nervous system (CNS) as made up of nonrenewable elements [1–3]. This finding, along with the characterization of adult neurogenesis in the olfactory bulb and hippocampus [3–5] triggered new hopes for brain repair. Yet, twenty years after, we realize that the dream of regenerative medicine applied to brain/spinal cord injuries and neurodegenerative diseases is still very far [6, 7]. As a matter of fact, adult neurogenesis in mammals occurs mainly within two restricted areas known as “neurogenic sites” [3, 8]: the forebrain subventricular zone (SVZ), reviewed in [9]; and the hippocampal dentate gyrus (subgranular zone, SGZ), reviewed in [10]. As a direct consequence of such topographical localization, most of the CNS parenchyma out of the two “classic” neurogenic sites remains substantially a nonrenewable tissue. An indirect proof of this statement resides in the fact that most of the traumatic/vascular injuries and neurodegenerative diseases, which actually occur in “nonneurogenic” regions, have still not found efficacious therapies capable of restoring CNS structure and functions through cell replacement. Thus, two decades
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