Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner.

NPI-Semel Institute for Neuroscience & Human Behavior and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell stem cell (Impact Factor: 22.15). 01/2011; 8(1):59-71. DOI: 10.1016/j.stem.2010.11.028
Source: PubMed

ABSTRACT 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 that may have significant implications for brain injury, disease, and repair.

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May 21, 2014