title: Resistance of glia-like central and peripheral neural stem cells to genetically induced mitochondrial dysfunction--differential effects on neurogenesis.
abstract: Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is unstudied. We have generated an animal model with homozygous deletion of the succinate dehydrogenase subunit D gene restricted to cells of glial fibrillary acidic protein lineage (hGFAP-SDHD mouse). Genetic mitochondrial damage did not alter the generation, maintenance, or multipotency of glia-like central NSCs. However, differentiation to neurons and oligodendrocytes (but not to astrocytes) was impaired and, hence, hGFAP-SDHD mice showed extensive brain atrophy. Peripheral neuronal populations were normal in hGFAP-SDHD mice, thus highlighting their non-glial (non hGFAP(+)) lineage. An exception to this was the carotid body, an arterial chemoreceptor organ atrophied in hGFAP-SDHD mice. The carotid body contains glia-like adult stem cells, which, as for brain NSCs, are resistant to genetic mitochondrial damage.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Díaz-Castro
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pardal
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: García-Flores
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Sobrino
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Durán
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain lbarneo@us.es jpiruat-ibis@us.es.
authors.forename: José I
authors.initials: JI
authors.lastname: Piruat
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío CSIC Universidad de Sevilla, Seville, Spain Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla, Spain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain lbarneo@us.es jpiruat-ibis@us.es.
authors.forename: José
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development; D002344:Carotid Body / Q000166:cytology / Q000648:ultrastructure; D004195:Disease Models, Animal; D017353:Gene Deletion; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D055495:Neurogenesis; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D013385:Succinate Dehydrogenase
keywords: carotid body stem cells; mitochondrial dysfunction; neural stem cells; peripheral versus central neurogenesis