Adult Neurogenesis Transiently Generates Oxidative Stress
Open Access
- 30 April 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (4), e35264
- https://doi.org/10.1371/journal.pone.0035264
Abstract
An increasing body of evidence suggests that alterations in neurogenesis and oxidative stress are associated with a wide variety of CNS diseases, including Alzheimer’s disease, schizophrenia and Parkinson’s disease, as well as routine loss of function accompanying aging. Interestingly, the association between neurogenesis and the production of reactive oxidative species (ROS) remains largely unexamined. The adult CNS harbors two regions of persistent lifelong neurogenesis: the subventricular zone and the dentate gyrus (DG). These regions contain populations of quiescent neural stem cells (NSCs) that generate mature progeny via rapidly-dividing progenitor cells. We hypothesized that the energetic demands of highly proliferative progenitors generates localized oxidative stress that contributes to ROS-mediated damage within the neuropoietic microenvironment. In vivo examination of germinal niches in adult rodents revealed increases in oxidized DNA and lipid markers, particularly in the subgranular zone (SGZ) of the dentate gyrus. To further pinpoint the cell types responsible for oxidative stress, we employed an in vitro cell culture model allowing for the synchronous terminal differentiation of primary hippocampal NSCs. Inducing differentiation in primary NSCs resulted in an immediate increase in total mitochondria number and overall ROS production, suggesting oxidative stress is generated during a transient window of elevated neurogenesis accompanying normal neurogenesis. To confirm these findings in vivo, we identified a set of oxidation-responsive genes, which respond to antioxidant administration and are significantly elevated in genetic- and exercise-induced model of hyperactive hippocampal neurogenesis. While no direct evidence exists coupling neurogenesis-associated stress to CNS disease, our data suggest that oxidative stress is produced as a result of routine adult neurogenesis.Keywords
This publication has 51 references indexed in Scilit:
- Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progressionNeurobiology of Aging, 2012
- Mitochondrial dysfunction and pathology in bipolar disorder and schizophreniaInternational Journal of Developmental Neuroscience, 2011
- Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's diseaseThe Lancet Neurology, 2011
- Oxidative stress in schizophrenia: An integrated approachNeuroscience & Biobehavioral Reviews, 2011
- A Protocol for Isolation and Enriched Monolayer Cultivation of Neural Precursor Cells from Mouse Dentate GyrusFrontiers in Neuroscience, 2011
- Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illnessJournal of Psychiatry and Neuroscience, 2010
- Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stressBMC Neuroscience, 2009
- Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disordersMolecular Brain, 2008
- Enriched Monolayer Precursor Cell Cultures from Micro-Dissected Adult Mouse Dentate Gyrus Yield Functional Granule Cell-Like NeuronsPLOS ONE, 2007
- Microarray analysis of oxidative stress regulated genes in mesencephalic dopaminergic neuronal cells: Relevance to oxidative damage in Parkinson's diseaseNeurochemistry International, 2007