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 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.
Shi
Jian
J
Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Miles
Darryl K
DK
Orr
Benjamin A
BA
Massa
Stephen M
SM
Kernie
Steven G
SG
D000818:Animals; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000172:deficiency*
D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D001973:Bromodeoxyuridine; D002118:Calcium