title: Resistance of subventricular neural stem cells to chronic hypoxemia despite structural disorganization of the germinal center and impairment of neuronal and oligodendrocyte survival.
abstract: Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia.
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors: Xavier
authors: X
authors: d'Anglemont de Tassigny
authors: Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; Network Center of Biomedical Research on Neurodegenerative Diseases (CIBERNED), Spain.
authors: M Salomé
authors: MS
authors: Sirerol-Piquer
authors: Laboratory of Regenerative Medicine, San Carlos Institute of Health Investigation, Madrid, Spain.
authors: Ulises
authors: U
authors: Gómez-Pinedo
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors: Ricardo
authors: R
authors: Pardal
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors: Sonia
authors: S
authors: Bonilla
authors: Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.
authors: Vivian
authors: V
authors: Capilla-Gonzalez
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors: Ivette
authors: I
authors: López-López
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors: Francisco Javier
authors: FJ
authors: De la Torre-Laviana
authors: Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; Network Center of Biomedical Research on Neurodegenerative Diseases (CIBERNED), Spain.
authors: José Manuel
authors: JM
authors: García-Verdugo
authors: Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain; Network Center of Biomedical Research on Neurodegenerative Diseases (CIBERNED), Spain.
authors: José
authors: J
authors: López-Barneo
keywords: chronic hypoxemia; neural stem cells; neuronal differentiation; oligodendrocyte survival; subventricular germinal niche; ultrastructure