Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

Abstract

Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain

“…While these observations do not rule out the possibility that OPCs can generate mature neurons, it may help explain the conclusion drawn by others that all DCX-positive cells, including those located outside of the dentate gyrus and subventricular zone, have neuronal attributes. These observations do not rule out the possibility of OPC-derived neurogenesis but they suggest additional caution to exclude other possibilities (see further discussion of this issue in Dimou and Gallo, 2015; Feliciano et al, 2015). …”

Distribution and fate of DCX/PSA-NCAM expressing cells in the adult mammalian cortex: A local reservoir for adult cortical neuroplasticity?

“…Some of these findings could not be replicated in certain mammalian species, while others could not be reproduced since their first publication or have since been contradicted by subsequent studies. It is also possible that some of these findings are based on low-level, "incomplete" neurogenic processes that protracted from embryogenesis into the postnatal period (reviewed in Bonfanti and Peretto, 2011;Feliciano et al, 2015). Despite the controversies, these cortical and subcortical areas are currently classified as the "non-canonical neurogenic regions" of the healthy mammalian brain (Bonfanti, 2013;Peretto and Bonfanti, 2014;Feliciano et al, 2015).…”

The birth of new neurons in the maternal brain: Hormonal regulation and functional implications

“…As compared to the DG and SVZ, far fewer numbers of new neurons are generated in these regions during adulthood although better detection methods are likely needed (Gould, 2007; Arisi et al, 2012; Inta et al, 2015; Nacher and Bonfanti, 2015; Schoenfeld and Cameron, 2015). Furthermore, many questions remain about newborn neurons in these areas including their origin (local or SVZ) and functions (Shapiro et al, 2009; Lee and Blackshaw, 2012; Feliciano et al, 2015; Inta et al, 2015). Nonetheless, a growing number of studies have revealed that neurogenesis in at least some of these areas is subject to modulation by a variety of physiological and environmental factors including pregnancy, pup exposure and parenting.…”