Klotho Regulates Postnatal Neurogenesis and Protects Against Age-related Spatial Memory Loss

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2017 Aug 25

PMID 28837861

Citations 27

Authors

Ann M Laszczyk

Stephanie Fox-Quick

Hai T Vo

Dailey Nettles

Phyllis C Pugh

Linda Overstreet-Wadiche

Gwendalyn D King

Affiliations

Soon will be listed here.

Abstract

Although the absence of the age-regulating klotho protein causes klotho-deficient mice to rapidly develop cognitive impairment and increasing klotho enhances hippocampal-dependent memory, the cellular effects of klotho that mediate hippocampal-dependent memory function are unknown. Here, we show premature aging of the klotho-deficient hippocampal neurogenic niche as evidenced by reduced numbers of neural stem cells, decreased proliferation, and impaired maturation of immature neurons. Klotho-deficient neurospheres show reduced proliferation and size that is rescued by supplementation with shed klotho protein. Conversely, 6-month-old klotho-overexpressing mice exhibit increased numbers of neural stem cells, increased proliferation, and more immature neurons with enhanced dendritic arborization. Protection from normal age-related loss of object location memory with klotho overexpression and loss of spatial memory when klotho is reduced by even half suggests direct, local effects of the protein. Together, these data show that klotho is a novel regulator of postnatal neurogenesis affecting neural stem cell proliferation and maturation sufficient to impact hippocampal-dependent spatial memory function.

Citing Articles

Calvo B, Schembri-Wismayer P, Duran-Alonso M Cells. 2025; 14(5).

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Celebi Z, Yazici E, Erdogan D, Davutoglu O, Yazici A BMC Psychiatry. 2025; 25(1):53.

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Association of serum klotho with cognitive function among individuals with nonalcoholic fatty liver disease.

Wu F, Pan J, Chen M, Lai X, Gu Y, Pei L Front Aging Neurosci. 2024; 16:1487182.

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Development of an α-Klotho Recognizing High-Affinity Peptide Probe from In-Solution Enrichment.

Zhang P, Ye X, Wang J, Smith C, Sousa S, Loas A JACS Au. 2024; 4(4):1334-1344.

PMID: 38665650 PMC: 11040699. DOI: 10.1021/jacsau.3c00650.

Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.

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