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

Autor:	Cai Y; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China.; Department of Histology and Embryology, Third Military Medical University, 400038 Chongqing, China., Tang X; Department of Histology and Embryology, Third Military Medical University, 400038 Chongqing, China., Chen X; School of Medicine, Nankai University, 300071 Tianjin, China., Li X; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Wang Y; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Bao X; Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, 400038 Chongqing, China., Wang L; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Sun D; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Zhao J; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Xing Y; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China., Warner M; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77054., Xu H; Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, 400038 Chongqing, China., Gustafsson JÅ; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77054; jgustafsson@uh.edu fanxiaotang2005@163.com.; Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institute, 141 86 Novum, Sweden., Fan X; Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, 400038 Chongqing, China; jgustafsson@uh.edu fanxiaotang2005@163.com.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Mar 20; Vol. 115 (12), pp. E2725-E2733. Date of Electronic Publication: 2018 Mar 05.
DOI:	10.1073/pnas.1800184115
Abstrakt:	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 β (LXRβ) 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 LXRβ 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 LXRβ-null mice. In addition, LXRβ deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRβ 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 LXRβ-deficient mice. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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