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Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Journal

Publisher

MDPI
DOI: 10.3390/ijms22073342

Keywords

adult neurogenesis; hippocampus; mitochondrial metabolism; mitochondrial dynamics; reactive oxygen species (ROS); autophagy; mitophagy; neurodegeneration; cognitive dysfunction; psychological stress; mood disorders

Funding

  1. China National Science Foundation [31970715]

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Adult neurogenesis is a highly regulated process generating new neurons in specific regions of the adult brain, with defects linked to cognitive decline and mood disorders. Understanding mechanisms regulating adult neurogenesis is crucial for improving preventative measures and therapies for these conditions. Mitochondria play a key role in regulating various aspects of adult neurogenesis, emphasizing the potential for targeting mitochondrial function in stem cell-based interventions for cognitive and mood disorders.
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.

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