Abstract
Adult neurogenesis is a multistage process by which neurons are generated and integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Neurogenesis plays a fundamental role in postnatal brain, where it is required for neuronal plasticity. Moreover, perturbation of adult neurogenesis contributes to several human diseases, including cognitive impairment and neurodegenerative diseases. The interplay between extrinsic and intrinsic factors is fundamental in regulating neurogenesis. Over the past decades, several studies on intrinsic pathways, including transcription factors, have highlighted their fundamental role in regulating every stage of neurogenesis. However, it is likely that transcriptional regulation is part of a more sophisticated regulatory network, which includes epigenetic modifications, non-coding RNAs and metabolic pathways. Here, we review recent findings that advance our knowledge in epigenetic, transcriptional and metabolic regulation of adult neurogenesis in the SGZ of the hippocampus, with a special attention to the p53-family of transcription factors.
Highlights
The development of the mammalian central nervous system (CNS) is a spatial and temporal regulated process that evolves from a small number of cells that proliferate, acquire regional identities and give rise to different cell types [1]
Adult neurogenesis is restricted in neurogenic niches that are localized in two different regions of the brain, the subventricular zone (SVZ) of the lateral ventricle where new neurons are generated and migrate to the olfactory bulb (OB), and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus [4,5,6]
Among the members of the p53 family, p73 is a key player in the regulation of CNS development and function by modulating neural stem cells (NSCs) self-renewal and differentiation as well as promoting terminal neuronal differentiation [140,141,142]
Summary
The development of the mammalian central nervous system (CNS) is a spatial and temporal regulated process that evolves from a small number of cells that proliferate, acquire regional identities and give rise to different cell types [1] These cells have been classified as neural stem cells (NSCs) and have the capability to produce identical NSCs progeny through symmetric cell division (self-renewal) and to differentiate into specialized brain cell types such as neurons, astrocytes and oligodendrocytes [2,3,4]. Stage 6 of adult neurogenesis occurs at approximately 4 weeks after birth and is the synaptic integration where newly generated neurons establish their synaptic contacts into the pre-existing circuits [8,9]. The present review discusses and summarises the recent research on adult neurogenesis to improve our understanding of the transcriptional, epigenetic and metabolic regulation of neurogenesis in the human brain
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