Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner

By J. L. Le Belle, N. M. Orozco, A. Paucar, Jonathan P. Saxe, J. Mottahedeh, A. Pyle, Hong Wu, H. Kornblum. Cell Stem Cell, 2011

746 citations recorded by the source corpus.

Summary The majority of research on reactive oxygen species (ROS) has focused on their cellular toxicities. Stem cells generally have been thought to maintain low levels of ROS as a protection against these processes. However, recent studies suggest that ROS can also play roles as second messengers, activating normal cellular processes. Here, we investigated ROS function in primary brain-derived neural progenitors. Somewhat surprisingly, we found that proliferative, self-renewing multipotent neural progenitors with the phenotypic characteristics of neural stem cells (NSC) maintained a high ROS status and were highly responsive to ROS stimulation. ROS-mediated enhancements in self-renewal and neurogenesis were dependent on PI3K/Akt signaling. Pharmacological or genetic manipulations that diminished cellular ROS levels also interfered with normal NSC and/or multipotent progenitor function both in vitro and in vivo. This study has identified a redox-mediated regulatory mechanism of NSC function which may have significant implications for brain injury, disease, and repair.

Subfields: Developmental Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/0f2e4b5a17e373d50c939421bfdd8e4fd30a0e77

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Citations in the corpus

ROS Function in Redox Signaling and Oxidative Stress (2014, background): “Similarly, lowering ROS levels decreases the regenerative capacity of neural stem cells and spermatogonial stem cells [145,146].”
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “To fine-tune the redox homeostasis that can either prohibit the damage by oxidative distress or maintain the physiologic ROS to sustain normal cellular processes, organisms have evolved a complex antioxidant defense system consisting of both enzymatic and non-enzymatic scavengers.(106,127,128) Intri”
Chemistry and biology of reactive oxygen species in signaling or stress responses (2011, background): “Concurrent with our work, another report documented that a population of neural stem cells located in the subventricular zone also use Nox2-derived ROS to modulate stem and progenitor pools and neurogenesi”