Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss

NEUROBIOLOGY OF AGING

卷:59

Article

Laszczyk, Ann M.¹  Fox-Quick, Stephanie¹  Vo, Hai T.¹  Nettles, Dailey¹  Pugh, Phyllis C.¹  Overstreet-Wadiche, Linda¹  King, Gwendalyn D.¹ 

[1] Univ Alabama Birmingham, Dept Neurobiol, 1825 Univ Blvd,Shelby 913, Birmingham, AL 35294 USA

关键词: Postnatal neurogenesis;    Hippocampus;    Neural stem cell;    Aging;    Cognition;   

DOI  :  10.1016/j.neurobiolaging.2017.07.008

来源: Elsevier

【 摘 要 】

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. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

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