Abstract
Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.
Highlights
Neurogenesis produces new neurons from neural stem cells (NSC) and is essential for brain development
Single-cell RNA sequencing revealed that quiescent NSC in the adult hippocampus rely on glycolysis and fatty acid oxidation (FAO) and have low protein synthesis, while oxidative phosphorylation (OXPHOS) and protein synthesis are upregulated during the transition of qNSC to become activated NSC and later intermediate progenitor cells (IPC) [56]
It might be proposed that mild mitochondrial dysfunction primarily compromises differentiation of adult-born neurons in the dentate gyrus (DG) due to absolute dependence of differentiated neurons on OXPHOS, while severe defects of mitochondrial bioenergetics impair NSPC proliferation and survival due to the increased dependence of IPC on mitochondrial metabolism
Summary
Neurogenesis produces new neurons from neural stem cells (NSC) and is essential for brain development. NSC and neurogenesis occur in two discrete regions of the adult brain: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of dentate gyrus (DG) in the hippocampus [1]. In these two areas, radial glia-like NSC self-renew or give rise to transiently proliferating intermediate progenitor cells (IPC) that subsequently form neuroblasts. Adult hippocampal neurogenesis (AHN) is important for spatial and contextual pattern separation, which requires the DG [5,6] and depends on immature, adult-born granule neurons that display increased excitability and plasticity [7,8,9]. The studies highlight the need for standardized procedures and better markers for neurogenesis when working with postmortem tissue [26,27,28,29]
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