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15q11 - 13重复小鼠(一种自闭症动物模型)的脑结构与社会行为的相关性

Correlations of brain structure with the social behavior of 15q11-13 duplication mice, an animal model of autism.

作者信息

Zhao Zhilei, Okada Naohiro, Yagishita Sho, Yahata Noriaki, Nitta Nobuhiro, Shibata Sayaka, Abe Yoshifumi, Morita Susumu, Kumagai Eureka, Tanaka Kenji F, Suhara Tetsuya, Takumi Toru, Kasai Kiyoto, Jinde Seiichiro

机构信息

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, Faculty of Medicine Bldg, The University of Tokyo, 1 #NC207, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

出版信息

Neurosci Res. 2024 Dec;209:42-49. doi: 10.1016/j.neures.2024.07.009. Epub 2024 Aug 2.

Abstract

Duplication of chromosome 15q11-13 has been reported to be one of the most frequent cytogenetic copy number variations in autism spectrum disorder (ASD), and a mouse model of paternal 15q11-13 duplication was generated, termed 15q dup mice. While previous studies have replicated some of the behavioral and brain structural phenotypes of ASD separately, the relationship between brain structure and behavior has rarely been examined. In this study, we performed behavioral experiments related to anxiety and social behaviors and magnetic resonance imaging (MRI) using the same set of 15q dup and wild-type mice. 15q dup mice showed increased anxiety and a tendency toward alterations in social behaviors, as reported previously, as well as variability in terms of sociability. MRI analysis revealed that a lower sociability index was correlated with a smaller gray matter volume in the right medial entorhinal cortex. These results may help to understand how variability in behavioral phenotypes of ASD arises even in individuals with the same genetic background and to determine the individual differences in neurodevelopmental trajectory correlated with specific brain structures that underlie these phenotypes.

摘要

据报道,15号染色体q11-13区域的重复是自闭症谱系障碍(ASD)中最常见的细胞遗传学拷贝数变异之一,并且构建了父源15q11-13重复的小鼠模型,称为15q重复小鼠。虽然先前的研究已经分别复制了一些ASD的行为和脑结构表型,但很少有人研究脑结构与行为之间的关系。在本研究中,我们使用同一组15q重复小鼠和野生型小鼠进行了与焦虑和社交行为相关的行为实验以及磁共振成像(MRI)。如先前报道的那样,15q重复小鼠表现出焦虑增加和社交行为改变的趋势,以及社交能力的变异性。MRI分析显示,社交能力指数较低与右侧内嗅皮质灰质体积较小相关。这些结果可能有助于理解即使在具有相同遗传背景的个体中,ASD行为表型的变异性是如何产生的,并确定与这些表型潜在的特定脑结构相关的神经发育轨迹的个体差异。

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