Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development.
Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development.
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海马 TERT 通过调节神经发育来调节空间记忆形成
DOI：
10.1016/j.stemcr.2017.06.014
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发表时间：
2017-08-08
影响因子：
5.9
通讯作者：
Zhu DY
中科院分区：
文献类型：
--
作者：
Zhou QG;Liu MY;Lee HW;Ishikawa F;Devkota S;Shen XR;Jin X;Wu HY;Liu Z;Liu X;Jin X;Zhou HH;Ro EJ;Zhang J;Zhang Y;Lin YH;Suh H;Zhu DY
记忆形成的分子机制仍然是一个谜。在这里，我们表明，端粒酶催化亚基，基因敲除（Tert−/−）导致空间记忆形成能力极差。成年海马齿状回中的TERT敲低会损害空间记忆过程，而过表达则会促进空间记忆过程。我们发现TERT在神经发育中起关键作用，包括海马新生神经元的树突发育和轴突发生。单突触假型狂犬病病毒逆行追踪方法表明，海马新生神经元的神经回路整合需要TERT。有趣的是，TERT以逆转录活性非依赖的方式调节神经发育和空间记忆形成。利用X射线照射，我们发现海马新生神经元通过TERT介导空间记忆过程的调制。这些观察结果揭示了TERT通过非经典途径的重要功能，并鼓励开发基于TERT的策略来治疗神经系统疾病相关的记忆障碍。Tert基因敲除导致空间记忆形成能力极差Tert−/−小鼠树突发育和轴突发生受损TERT是海马新生神经元神经回路整合所必需的TERT以不依赖于活性的方式调节空间记忆形成在这篇文章中，Qi-Gang Zhou和同事表明，空间记忆形成，神经发育，包括树突发育和轴突发生，和神经回路整合受损。海马TERT以逆转录活性独立的方式解释这些表型。
The molecular mechanism of memory formation remains a mystery. Here, we show that TERT, the catalytic subunit of telomerase, gene knockout (Tert−/−) causes extremely poor ability in spatial memory formation. Knockdown of TERT in the dentate gyrus of adult hippocampus impairs spatial memory processes, while overexpression facilitates it. We find that TERT plays a critical role in neural development including dendritic development and neuritogenesis of hippocampal newborn neurons. A monosynaptic pseudotyped rabies virus retrograde tracing method shows that TERT is required for neural circuit integration of hippocampal newborn neurons. Interestingly, TERT regulated neural development and spatial memory formation in a reverse transcription activity-independent manner. Using X-ray irradiation, we find that hippocampal newborn neurons mediate the modulation of spatial memory processes by TERT. These observations reveal an important function of TERT through a non-canonical pathway and encourage the development of a TERT-based strategy to treat neurological disease-associated memory impairment. Tert gene knockout causes extremely poor ability in spatial memory formation Dendritic development and neuritogenesis are impaired in Tert−/− mice TERT is required for neural circuit integration of hippocampal newborn neurons TERT regulates spatial memory formation in an activity-independent manner In this article, Qi-Gang Zhou and colleagues show that spatial memory formation, neural development including dendritic development and neuritogenesis, and neural circuit integration are impaired in Tert gene knockout mice. Hippocampal TERT accounts for these phenotypes in a reverse transcription activity-independent manner.
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影响因子：
4.6
作者：
Ferrón, S;Mira, H;Blasco, MA
通讯作者：
Blasco, MA
DOI：
10.1073/pnas.1013004108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Montgomery, Robert K.;Carlone, Diana L.;Breault, David T.
通讯作者：
Breault, David T.
影响因子：
16.2
作者：
Osakada F;Mori T;Cetin AH;Marshel JH;Virgen B;Callaway EM
通讯作者：
Callaway EM
影响因子：
64.8
作者：
Park, Jae-Il;Venteicher, Andrew S.;Hong, Ji Yeon;Choi, Jinkuk;Jun, Sohee;Shkreli, Marina;Chang, Woody;Meng, Zhaojing;Cheung, Peggie;Ji, Hong;McLaughlin, Margaret;Veenstra, Timothy D.;Nusse, Roel;McCrea, Pierre D.;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
DOI：
10.1073/pnas.0601992103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori