Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse
Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse
复制标题
肝脏X受体β调节小鼠齿状回的发育和自闭症样行为
DOI：
10.1073/pnas.1800184115
复制
发表时间：
2018-03-20
影响因子：
11.1
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
--
作者：
Cai, Yulong;Tang, Xiaotong;Fan, Xiaotang
海马的齿状回（DG）是一个分层的大脑区域，其中神经发生在胚胎发育早期开始并持续到成年。最近的研究表明，DG神经发生的缺陷似乎与自闭症谱系障碍（ASD）样行为的发生有关。肝脏X受体β（LXR β）最近作为参与层压CNS结构发育的重要转录因子出现，但关于其在DG发育中的作用知之甚少。在这里，我们表明，在小鼠中的LXR β的缺失导致发育不全的DG，包括异常的祖细胞和颗粒细胞分化的形成。我们还发现，Notch 1的表达，祖细胞自我更新的中央介质，在LXR β-null小鼠减少。此外，小鼠中的LXR β缺失导致自闭症样行为，包括异常的社会互动和重复行为。这些数据揭示了LXR β在协调DG内神经祖细胞及时分化中的核心作用，从而为LXR β缺陷小鼠中自闭症相关行为的发生提供了可能的解释。
The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor beta (LXR beta) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXR beta in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXR beta-null mice. In addition, LXR beta deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXR beta in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXR beta-deficient mice.