神经发生
抛物线性
海马结构
神经干细胞
认知功能衰退
海马体
神经科学
生物
干细胞
异时
细胞生物学
内分泌学
内科学
医学
个体发育
疾病
痴呆
作者
Géraldine Gontier,Manasi Iyer,Jeremy Shea,Gregor Bieri,Elizabeth Wheatley,Miguel Ramalho-Santos,Saul Villeda
出处
期刊:Cell Reports
[Elsevier]
日期:2018-02-01
卷期号:22 (8): 1974-1981
被引量:138
标识
DOI:10.1016/j.celrep.2018.02.001
摘要
Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation.
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