自闭症激酶不活跃 Met 小鼠模型的前脑功能连接性和神经传递发生改变

IF 2.2 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS
Shiyu Tang, Elizabeth M Powell, Wenjun Zhu, Fu-Sun Lo, Reha S Erzurumlu, Su Xu
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引用次数: 0

摘要

编码肝细胞生长因子酪氨酸激酶受体的基因MET是自闭症谱系障碍(ASD)的易感基因。具有激酶活性的MET基因改变小鼠为了解自闭症神经回路组织变化提供了一个潜在模型。在这里,我们重点研究体感丘脑皮层回路,因为自闭症谱系障碍伴有明显的体感敏感表型,而这一系统在小鼠的感觉运动和社交行为中扮演着重要角色。我们采用静息态功能磁共振成像和体内高分辨率质子磁共振波谱检查了野生型、杂合子Met-Emx1和完全非活性同合子Met-Emx1小鼠的神经元连接和神经传递。与野生型对照组相比,Met-Emx1大脑的大规模体感网络连接成熟度受损。在网络特征和谷氨酸/γ-氨基丁酸(GABA)平衡方面,观察到显著的性别×基因型交互作用。与野生型大脑相比,雌性 Met-Emx1 大脑在躯体感觉丘脑皮层系统中显示出显著的连接性和谷氨酸/GABA 平衡变化。在杂合子 Met-Emx1 雌性大脑中,丘脑中的谷氨酸/GABA 比率与躯体感觉皮层和丘脑之间的连接性相关。研究结果支持这样的假设,即体感丘脑皮层系统的异常功能是在 Met-Emx1 小鼠身上观察到的明显体感行为表型的核心。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.

Altered Forebrain Functional Connectivity and Neurotransmission in a Kinase-Inactive Met Mouse Model of Autism.

MET, the gene encoding the tyrosine kinase receptor for hepatocyte growth factor, is a susceptibility gene for autism spectrum disorder (ASD). Genetically altered mice with a kinase-inactive Met offer a potential model for understanding neural circuit organization changes in autism. Here, we focus on the somatosensory thalamocortical circuitry because distinct somatosensory sensitivity phenotypes accompany ASD, and this system plays a major role in sensorimotor and social behaviors in mice. We employed resting-state functional magnetic resonance imaging and in vivo high-resolution proton MR spectroscopy to examine neuronal connectivity and neurotransmission of wild-type, heterozygous Met-Emx1, and fully inactive homozygous Met-Emx1 mice. Met-Emx1 brains showed impaired maturation of large-scale somatosensory network connectivity when compared with wild-type controls. Significant sex × genotype interaction in both network features and glutamate/gamma-aminobutyric acid (GABA) balance was observed. Female Met-Emx1 brains showed significant connectivity and glutamate/GABA balance changes in the somatosensory thalamocortical system when compared with wild-type brains. The glutamate/GABA ratio in the thalamus was correlated with the connectivity between the somatosensory cortex and the thalamus in heterozygous Met-Emx1 female brains. The findings support the hypothesis that aberrant functioning of the somatosensory thalamocortical system is at the core of the conspicuous somatosensory behavioral phenotypes observed in Met-Emx1 mice.

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来源期刊
Molecular Imaging
Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
期刊介绍: Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.
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