Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning
Telencephalon-specific Alkbh1 conditional knockout mice display hippocampal atrophy and impaired learning
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DOI：
10.1002/1873-3468.14098
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发表时间：
2021-05-19
期刊：
影响因子：
3.5
通讯作者：
Aiba, Atsu
中科院分区：
文献类型：
--
作者：
Kawarada, Layla;Fukaya, Masahiro;Aiba, Atsu
AlkB同源物1 （ALKBH1）负责线粒体tRNA（Met）上5-甲酰基胞苷（f(5)C）的生物生成，对线粒体蛋白质合成至关重要。大脑，尤其是海马体，非常容易受到线粒体功能障碍的影响；因此，维持线粒体活性对于预防与海马功能障碍相关的疾病是非常必要的。为了研究ALKBH1在海马中的作用，我们在近交C57BL/6背景下培养了背端脑特异性ALKBH1条件敲除（cKO）小鼠。这些小鼠表现出呼吸链复合物活性降低、海马萎缩和CA1锥体神经元异常。此外，cKO小鼠的恐惧条件反射和Morris水迷宫实验结果表明，海马异常导致海马依赖学习功能受损。这些发现表明ALKBH1在海马中的关键作用。
AlkB homolog 1 (ALKBH1) is responsible for the biogenesis of 5-formylcytidine (f(5)C) on mitochondrial tRNA(Met) and essential for mitochondrial protein synthesis. The brain, especially the hippocampus, is highly susceptible to mitochondrial dysfunction; hence, the maintenance of mitochondrial activity is strongly required to prevent disorders associated with hippocampal malfunction. To study the role of ALKBH1 in the hippocampus, we generated dorsal telencephalon-specific Alkbh1 conditional knockout (cKO) mice in inbred C57BL/6 background. These mice showed reduced activity of the respiratory chain complex, hippocampal atrophy, and CA1 pyramidal neuron abnormalities. Furthermore, performances in the fear-conditioning and Morris water maze tests in cKO mice indicated that the hippocampal abnormalities led to impaired hippocampus-dependent learning. These findings indicate critical roles of ALKBH1 in the hippocampus.