文章基本信息

标题：Cell-density-dependent regulation of neural precursor cell function
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作者：Charles L. Limoli ; Radoslaw Rola ; Erich Giedzinski 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：45
页码：16052-16057
DOI：10.1073/pnas.0407065101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Stress-induced reductions of neural precursor cells from the subgranular zone of the hippocampal dentate gyrus have been linked to impaired neurogenesis and cognitive dysfunction. Given the importance of redox state in regulating multiple damage-responsive pathways in the CNS, we hypothesize that oxidative stress plays a major role in affecting neurogenesis and subsequent cognitive function after cell injury/depletion. Using an in vitro system, we showed that the level of reactive oxygen species (ROS), which depend critically on changes in cell density, were significantly higher in neural precursor cells when compared with other primary and transformed cell lines. ROS were significantly elevated ({approx}4-fold) under low- (<1 x 104 cells per cm2) versus high-density (>1 x 105 cells per cm2) conditions. Higher ROS levels found at lower cell densities were associated with elevated proliferation and increased metabolic activity. These ROS were likely a result of altered mitochondrial function that ultimately compromised the growth rate of cells. At high cell densities, intracellular ROS and oxidative damage were reduced in concert with an increased expression of mitochondrial superoxide dismutase 2. Our finding that DNA-damage-induced depletion of neural precursor cells in the subgranular zone of mice also led to increased ROS and altered proliferation validated our in vitro system. Increased ROS and proliferation associated with the reduction of precursor cell numbers both in vitro and in vivo could be reversed with the antioxidant {alpha}-lipoic acid. These data showed that neural precursor cells were predisposed to microenvironmental cues that regulate redox-sensitive pathways to control cellular proliferation after CNS damage.