Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus.

Autor:	Salech F; Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile.; Biomedical Neuroscience Institute (BNI), Santiago, Chile.; Unidad de Geriatría, Hospital Clínico Universidad de Chile, Santiago.; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago., Varela-Nallar L; Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile., Arredondo SB; Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile., Bustamante DB; Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile., Andaur GA; Centro de Investigaciones Biomédicas (CIB), Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile., Cisneros R; Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile., Ponce DP; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago., Ayala P; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago., Inestrosa NC; Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago.; Center for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile., Valdés JL; Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile.; Biomedical Neuroscience Institute (BNI), Santiago, Chile., I Behrens M; Centro de Investigación Clínica Avanzada (CICA), Hospital Clínico Universidad de Chile, Santiago.; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago.; Clínica Alemana de Santiago, Chile., Couve A; Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago, Chile.; Biomedical Neuroscience Institute (BNI), Santiago, Chile.
Jazyk:	angličtina
Zdroj:	The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2019 Jun 18; Vol. 74 (7), pp. 1043-1051.
DOI:	10.1093/gerona/glx248
Abstrakt:	Klotho is an aging-related protein associated with hippocampal cognitive performance in mammals. Klotho regulates progenitor cell proliferation in non-neuronal tissues, but its role in adult hippocampal neurogenesis (AHN) has not been explored. Klotho expression in the adult mouse hippocampus was examined by immunofluorescence and polymerase chain reaction. AHN was evaluated in the hippocampus of klotho knock-out mice (KO), klotho KO/vitamin D-receptor mutant mice, and in a model of local klotho hippocampal knockdown. The recombinant Klotho effect on proliferation was measured in mouse-derived hippocampal neural progenitor cells. Hippocampal-dependent memory was assessed by a dry-land version of the Morris water maze. Klotho was expressed in the granular cell layer of the adult Dentate Gyrus. AHN was increased in klotho KO mice, but not in klotho KO/vitamin D-receptor mutant mice. Inversely, local downregulation of hippocampal Klotho diminished AHN. Recombinant Klotho increased the proliferation rate of neural progenitors. Downregulation of hippocampal Klotho correlated with a decreased performance in hippocampal-dependent memory. These results suggest that Klotho directly participates in regulating AHN. Our observations indicate that Klotho promotes proliferation, AHN and hippocampal-dependent cognition. Increased neurogenesis in klotho KO mice may be secondary to the activation of other pathways altered in the model, such as vitamin D. (© The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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