Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

dc.creatorSalech-Morales, Felipe
dc.creatorVarela-Nallar, Lorena Patricia
dc.creatorArredondo-Barros, Sebastián Ignacio
dc.creatorBustamante, Daniel B
dc.creatorAndaur, Gabriela A
dc.creatorCisneros-Contreras, Rodrigo
dc.creatorPonce, Daniela P
dc.creatorAyala, Patricia
dc.creatorInestrosa, Nibaldo C
dc.creatorValdes, José L
dc.creatorBehrens, María I
dc.creatorCouve-Correa, Andrés Oscar
dc.date2021-08-23T22:52:50Z
dc.date2022-07-08T20:34:59Z
dc.date2021-08-23T22:52:50Z
dc.date2022-07-08T20:34:59Z
dc.date2019
dc.date.accessioned2023-08-21T23:11:34Z
dc.date.available2023-08-21T23:11:34Z
dc.identifier1150933
dc.identifier1150933
dc.identifierhttps://hdl.handle.net/10533/251040
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8294011
dc.descriptionKlotho 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.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.1093/gerona/glx248
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleLocal Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus
dc.titleJOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


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