Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss.
Klotho regulates postnatal neurogenesis and protects against age-related spatial memory loss.
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DOI：
10.1016/j.neurobiolaging.2017.07.008
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发表时间：
2017-11
影响因子：
4.2
通讯作者：
King GD
中科院分区：
文献类型：
--
作者：
Laszczyk AM;Fox-Quick S;Vo HT;Nettles D;Pugh PC;Overstreet-Wadiche L;King GD
虽然缺乏年龄调节klotho蛋白会导致klotho缺陷小鼠迅速发展为认知障碍，并且增加klotho会增强记忆依赖性记忆，但klotho介导记忆依赖性记忆功能的细胞效应尚不清楚。在这里，我们显示了klotho缺陷海马神经原性生态位的过早老化，神经干细胞数量减少，增殖减少，未成熟神经元成熟受损。Klotho缺陷的神经球显示出减少的增殖和大小，这是通过补充脱落的Klotho蛋白来挽救的。相反，6个月大的klotho过表达小鼠表现出神经干细胞数量增加，增殖增加，以及具有增强的树突状分支的更多未成熟神经元。klotho过度表达对正常年龄相关的物体位置记忆丧失的保护作用以及klotho减少一半时空间记忆丧失的保护作用表明该蛋白质的直接局部作用。总之，这些数据表明，klotho是一种新的产后神经发生调节剂，影响神经干细胞增殖和成熟，足以影响海马依赖的空间记忆功能。
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 suggest 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.
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DOI：
10.1002/ar.22746
发表时间：
2013-09-01
影响因子：
2
作者：
Gil-Perotin, Sara;Duran-Moreno, Maria;Manuel Garcia-Verdugo, Jose
通讯作者：
Manuel Garcia-Verdugo, Jose
影响因子：
3.3
作者：
Hermann, Dirk M.;Kribben, Andreas;Bruck, Heike
通讯作者：
Bruck, Heike
DOI：
10.1093/gerona/63.12.1289
发表时间：
2008-12-01
影响因子：
5.1
作者：
Ishii, Masaki;Yamaguchi, Yasuhiro;Ouchi, Yasuyoshi
通讯作者：
Ouchi, Yasuyoshi
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
2
作者：
Haettig, Jakob;Stefanko, Daniel P.;Wood, Marcelo A.
通讯作者：
Wood, Marcelo A.