Injury-induced neurogenesis in Bax-deficient mice: evidence for regulation by voltage-gated potassium channels

Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro‐apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax‐deficient mice that have undergone traumatic brain injury, we find increased numbers of neur...

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Bibliographic Details
Published in:The European journal of neuroscience 2007-06, Vol.25 (12), p.3499-3512
Main Authors: Shi, Jian, Miles, Darryl K., Orr, Benjamin A., Massa, Stephen M., Kernie, Steven G.
Format: Article
Language:English
Subjects:
Animals
apoptosis
bcl-2-Associated X Protein - deficiency
Brain Injuries - pathology
Brain Injuries - physiopathology
Bromodeoxyuridine - metabolism
calcium
Calcium - metabolism
caspase
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Proliferation
Cells, Cultured
dentate gyrus
Female
Flow Cytometry - methods
Gene Expression Regulation - drug effects
Green Fluorescent Proteins - biosynthesis
Hippocampus - pathology
In Situ Nick-End Labeling - methods
Membrane Potentials - drug effects
Membrane Potentials - physiology
Membrane Potentials - radiation effects
Mice
Mice, Knockout
Nerve Tissue Proteins - metabolism
neural stem cell
Neurons - physiology
Potassium Channels, Voltage-Gated - physiology
Potassium Chloride - pharmacology
Stem Cells - metabolism
Stem Cells - pathology
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Summary:Adult neural stem and progenitor cells may help remodel the brain in response to injury. The pro‐apoptotic molecule Bax has recently been identified as a key player in adult neural stem cell survival. In Bax‐deficient mice that have undergone traumatic brain injury, we find increased numbers of neural progenitor cells in the dentate gyrus and improved remodeling of the hippocampus. Exogenous potassium chloride mimics spreading depression (SD)‐like events in vitro, and Bax‐deficient neural stem cells proliferate in response to these events more robustly than wild‐type neural stem cells. Selective potassium channel blockers interrupt SD‐mediated stimulation of stem cells. In addition, the potassium channel Kv4.1 is expressed within neural stem and progenitor cells in the dentate gyrus and is increased in Bax‐deficiency. These data suggest that the neuroprotection observed after injury in Bax‐deficiency may be due to increased neurogenesis via activation of the Kv4 family of potassium channels.
ISSN:0953-816X
1460-9568
DOI:10.1111/j.1460-9568.2007.05624.x