Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities
Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities
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DOI：
10.1038/nn.3151
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发表时间：
2012-08-01
影响因子：
25
通讯作者：
Bading, Hilmar
中科院分区：
文献类型：
--
作者：
Oliveira, Ana M. M.;Hemstedt, Thekla J.;Bading, Hilmar
认知能力在正常衰老过程中会下降，但其潜在的分子机制却知之甚少。我们发现，衰老与海马中DNA甲基转移酶Dnmt3a2表达的减少有关，而挽救Dnmt3a2水平可以恢复认知功能。此外，我们发现，Dnmt3a2是一种活性调节的立即早期基因，部分依赖于核钙信号，海马Dnmt3a2水平决定了年轻成年和老年小鼠的认知能力。
Cognitive abilities decline in normal aging, yet the underlying molecular mechanisms are poorly understood. We found that aging was associated with a decrease in the expression of the DNA methyltransferase Dnmt3a2 in the hippocampus and that rescuing Dnmt3a2 levels restored cognitive functions. Moreover, we found that Dnmt3a2 is an activity-regulated immediate early gene that is partly dependent on nuclear calcium signaling and that hippocampal Dnmt3a2 levels determine cognitive abilities in both young adult and aged mice.