Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus

Felipe Salech, Lorena Varela-Nallar, Sebastián B. Arredondo, Daniel B. Bustamante, Gabriela A. Andaur, Rodrigo Cisneros, Daniela P. Ponce, Patricia Ayala, Nibaldo C. Inestrosa, José L. Valdés, María I. Behrens, Andrés Couve

Resultado de la investigación: Article

2 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)1043-1051
Número de páginas9
PublicaciónJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volumen74
N.º7
DOI
EstadoPublished - 18 jun 2019

Huella dactilar

Neurogenesis
Hippocampus
Knockout Mice
Calcitriol Receptors
Stem Cells
Down-Regulation
Dentate Gyrus
Vitamin D
Cognition
Fluorescent Antibody Technique
Mammals
Cell Proliferation
Polymerase Chain Reaction
Water
Proteins

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Citar esto

Salech, Felipe ; Varela-Nallar, Lorena ; Arredondo, Sebastián B. ; Bustamante, Daniel B. ; Andaur, Gabriela A. ; Cisneros, Rodrigo ; Ponce, Daniela P. ; Ayala, Patricia ; Inestrosa, Nibaldo C. ; Valdés, José L. ; Behrens, María I. ; Couve, Andrés. / Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus. En: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2019 ; Vol. 74, N.º 7. pp. 1043-1051.
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title = "Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus",
abstract = "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.",
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author = "Felipe Salech and Lorena Varela-Nallar and Arredondo, {Sebasti{\'a}n B.} and Bustamante, {Daniel B.} and Andaur, {Gabriela A.} and Rodrigo Cisneros and Ponce, {Daniela P.} and Patricia Ayala and Inestrosa, {Nibaldo C.} and Vald{\'e}s, {Jos{\'e} L.} and Behrens, {Mar{\'i}a I.} and Andr{\'e}s Couve",
year = "2019",
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doi = "10.1093/gerona/glx248",
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Salech, F, Varela-Nallar, L, Arredondo, SB, Bustamante, DB, Andaur, GA, Cisneros, R, Ponce, DP, Ayala, P, Inestrosa, NC, Valdés, JL, Behrens, MI & Couve, A 2019, 'Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 74, n.º 7, pp. 1043-1051. https://doi.org/10.1093/gerona/glx248

Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus. / Salech, Felipe; Varela-Nallar, Lorena; Arredondo, Sebastián B.; Bustamante, Daniel B.; Andaur, Gabriela A.; Cisneros, Rodrigo; Ponce, Daniela P.; Ayala, Patricia; Inestrosa, Nibaldo C.; Valdés, José L.; Behrens, María I.; Couve, Andrés.

En: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 74, N.º 7, 18.06.2019, p. 1043-1051.

Resultado de la investigación: Article

TY - JOUR

T1 - Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus

AU - Salech, Felipe

AU - Varela-Nallar, Lorena

AU - Arredondo, Sebastián B.

AU - Bustamante, Daniel B.

AU - Andaur, Gabriela A.

AU - Cisneros, Rodrigo

AU - Ponce, Daniela P.

AU - Ayala, Patricia

AU - Inestrosa, Nibaldo C.

AU - Valdés, José L.

AU - Behrens, María I.

AU - Couve, Andrés

PY - 2019/6/18

Y1 - 2019/6/18

N2 - 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.

AB - 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.

KW - Adult hippocampal neurogenesis

KW - Cell proliferation

KW - Hippocampal-dependent cognition

KW - Stem cells

KW - Vitamin D

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U2 - 10.1093/gerona/glx248

DO - 10.1093/gerona/glx248

M3 - Article

VL - 74

SP - 1043

EP - 1051

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 7

ER -