Proliferative Neural Stem Cells Have High Endogenous ROS Levels that Regulate Self-Renewal and Neurogenesis in a PI3K/Akt-Dependant Manner
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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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Reactive oxygen species can increase stem cell self-renewal and neurogenesis through reversible inactivation of PTEN and hyper-activation of the NADPH oxidase (NOX)-PI3K pathway, which ultimately during early post-natal development will result in enlarged brains and autistic behaviors.
“Reactive oxygen species (ROS) can increase stem cell self-renewal and neurogenesis through the reversible inactivation of PTEN and hyper-activation of the NADPH oxidase (NOX)-PI3K pathway [134], which ultimately, during early post-natal development, will result in enlarged brains and autistic behaviors.”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [134]
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- Authors
- Le Belle, J. E., Orozco, N. M., Paucar, A. A., Saxe, J. P., Mottahedeh, J., Pyle, A. D., Wu, H., & Kornblum, H. I.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Kornblum, Harley I.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 8
- Issue
- 1
- Pages
- 59-71
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC3018289
- OpenAlex
- W1995168386
- Cited by
- 789
- References
- 53
- Citations by year
- 2026: 27 · 2025: 40 · 2024: 40 · 2023: 40 · 2022: 58 · 2021: 71 · 2020: 51 · 2019: 55 · 2018: 50 · 2017: 61 · 2016: 56 · 2015: 64 · 2014: 64 · 2013: 54 · 2012: 38
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks (AS1986, AS4954)
- National Institute of Mental Health (R01MH065756, MH65756)
- National Cancer Institute (CA-16 042, P30CA016042)
- National Institute of Allergy and Infectious Diseases (AI-28 697, P30AI028697)
- National Institute of Neurological Disorders and Stroke (R01NS052563)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD055784)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- reactive oxygen species, neural stem cells, neural progenitor cells, self-renewal, neurogenesis, PI3K/Akt signaling, redox signaling, second messengers, brain injury repair
- MeSH terms
- Animals, Cells, Cultured, Humans, Mice, Inbred Strains, Signal Transduction, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Neurogenesis, Neural Stem Cells
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