Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse

被引：38

作者：

Cai, Yulong ^{[1
,2
]}

Tang, Xiaotong ^{[2
]}

Chen, Xi ^{[3
]}

Li, Xin ^{[1
]}

Wang, Ying ^{[1
]}

Bao, Xiaohang ^{[4
]}

Wang, Lian ^{[1
]}

Sun, Dayu ^{[1
]}

Zhao, Jinghui ^{[1
]}

Xing, Yan ^{[1
]}

Warner, Margaret ^{[5
]}

Xu, Haiwei ^{[6
]}

Gustafsson, Jan-Ake ^{[5
,7
]}

Fan, Xiaotang ^{[1
]}

机构：

[1] Third Mil Med Univ, Sch Psychol, Dept Dev Neuropsychol, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, Dept Histol & Embryol, Chongqing 400038, Peoples R China

[3] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

[4] Third Mil Med Univ, Xinqiao Hosp, Dept Anesthesiol, Chongqing 400038, Peoples R China

[5] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX 77054 USA

[6] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Chongqing 400038, Peoples R China

[7] Karolinska Inst, Ctr Innovat Med, Dept Biosci & Nutr, S-14186 Novum, Sweden

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 12期

基金：

瑞典研究理事会; 中国国家自然科学基金;

关键词：

LXR beta; dentate gyrus; development; progenitor cells; autism; RADIAL GLIAL-CELLS; NEURAL STEM-CELLS; NEURONAL PROGENITORS; NEUROGENESIS; REELIN; DIFFERENTIATION; ORGANIZATION; CHOLESTEROL; EXPRESSION; MIGRATION;

D O I：

10.1073/pnas.1800184115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：E2725 / E2733

页数：9