A developmental perspective on adult hippocampal neurogenesis

Abstract

The generation of new neurons from neural stem cells (NSCs) throughout adult life in the mammalian brain is a biological process that fascinates scientists for its uniqueness and restorative potential. In the dentate gyrus (DG) of the hippocampus NSCs are able to self-renew and generate new granule cells and astrocytes through a complex and plastic mechanism that can be regulated by endogenous and exogenous cues at different levels. Unexpected recent findings suggest that the population of NSCs is heterogeneous in morphology and behavior. We herein explore the hypothesis that NSC heterogeneity and the neurogenic potential of the DG depends on their developmental origin. We provide an up-to-date picture of the process of neurogenesis in the adult hippocampus with an especial focus on NSCs and outline key unsolved aspects. Further, we discuss the origin of NSCs in the adult DG from a developmental perspective and explore the possibility of NSC heterogeneity being determined from early postnatal periods and being responsible for the neurogenic output of the DG in the long term.

Keywords: 5-bromo-2′-deoxyuridine; ANP; Aging; BLBP; BMP-receptor 1A; BMPR-1A; BMPs; BrdU; DCX; DG; Dentate gyrus; Development; ECS; GCL; GFAP; GFP; GLAST; KA; NB; NSCs; Neural stem cells; Neurogenesis; PSA-NCAM; QNP; RGCs; amplifying neural progenitors; astrocyte-specific glutamate transporter; bone morphogenetic proteins; brain lipid-binding protein; dentate gyrus; doublecortin; electroconvulsive shock; glial fibrillary acidic protein; granule cell layer; green fluorescent protein; kainic acid; neural stem cells; neuroblasts; non radial/horizontal NSCs; nr/hNSC; polysialic acid neural cell adhesion molecule; quiescent neural progenitors; rNSCs; radial glia cells; radial glia-like cells NSCs.