Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

Abstract

Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade.

Age-related decline in BubR1 impairs adult hippocampal neurogenesis

“…The hippocampus is one neurogenic niche where new neurons arising from neural stem cells (NSCs) are constantly generated throughout life in a process called adult hippocampal neurogenesis (Ming & Song, 2011). Deficits in this process are observed with aging and are believed to underlie age‐related cognitive deficits (van Praag et al ., 2005).…”

Cellules souches neurales et signalisation Notch

“…Dans le cerveau adulte, deux principales régions contiennent des CSN. Il s'agit de la zone sous-ventriculaire (ZSV) bordant la paroi des ventricules latéraux et de la zone sous-granulaire (ZSG) du gyrus denté de l'hippocampe [1,46] [3]. Dans des modèles d'ischémie, de démyélinisation ou de lésion corticale développés chez le rongeur, les CSN de la ZSV quittent leur état de quiescence.…”

Neurogenic hypothesis and psychiatric disorders

“…The term "neurogenesis" is a process which is defined as the ability of the precursor cells to generate functional neurons within the central nervous system (CNS) [11]. This process has been previously believed to occur only during the embryonic development and the early postnatal period, but not in the adult CNS.…”

“…These immature neurons can then be differentiated into dentate granule cells within the hippocampus. At a later stage, the dendrites gradually extend towards the molecular layer of the dentate gyrus with the establishment of synapses which can then integrate to the existing hippocampal-dependent neural circuit [11]. Very similar to the neurogenesis within the dentate gyrus, the activation of the radial glia-like cells which reside in the subventricular zone can cause proliferation of the transient amplifying cells and in turn, cause the generation of the migrating neuroblasts.…”

“…However, at this stage, rather than migrating a short distance to the granular cell layer within the dentate gyrus, the immature neurons differentiate into neuroblasts within the subventricular zone and are able to migrate in a chain manner via the rostral migratory stream (RMS) pathway to the olfactory bulb. Upon the arrival to the olfactory bulb, maturation of the periglomerular neurons and granule cells will occur with synaptic formation which can be functionally integrated to the neural circuit of the olfactory system [11]. Other than the neuronal lineage, the progenitor cells within these regions can differentiate into glial cells, such as the progenitors derived from the hippocampus have been found to differentiate into oligodendrocytes and astrocytes in cell culture [2].…”