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利用聚焦离子束铣削和扫描电子显微镜对具有15q11 - 13拷贝数变异的自闭症小鼠模型中的突触形态进行纳米级分析。

Nano-scale analysis of synapse morphology in an autism mouse model with 15q11-13 copy number variation using focused ion beam milling and scanning electron microscopy.

作者信息

Sato Yuka, Okabe Shigeo

机构信息

Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

出版信息

Microscopy (Oxf). 2019 Apr 1;68(2):122-132. doi: 10.1093/jmicro/dfy128.

Abstract

Circuit-level alternations in patients of autism spectrum disorder (ASD) is under active investigation and detailed characterization of synapse morphology in ASD model mice should be informative. We utilized focused ion beam milling and scanning electron microscopy (FIB-SEM) to obtain three-dimensional images of synapses in the layer 2/3 of the somatosensory cortex from a mouse model for ASD with human 15q11-13 chromosomal duplication (15q dup mice). We found a trend of higher spine density and a higher fraction of astrocytic contact with both spine and shaft synapses in 15q dup mice. Measurement of spine synapse structure indicated that the size of the post-synaptic density (PSD), spine head volume, spine head width and spine neck width were smaller in 15q dup mice. Categorization of spine synapses into five classes suggested a trend of less frequent mushroom spines in 15q dup mice. These results suggest relative increase in excitatory synapses with immature morphology but more astrocytic contacts in 15q dup mice, which may be linked to enhanced synapse turnover seen in ASD mouse models.

摘要

自闭症谱系障碍(ASD)患者的电路水平改变正在积极研究中,对ASD模型小鼠突触形态的详细表征应该会提供有用信息。我们利用聚焦离子束铣削和扫描电子显微镜(FIB-SEM)从具有人类15q11-13染色体重复的ASD小鼠模型(15q重复小鼠)中获取体感皮层第2/3层突触的三维图像。我们发现15q重复小鼠中存在棘密度更高以及星形胶质细胞与棘突触和轴突突触接触比例更高的趋势。棘突触结构测量表明,15q重复小鼠的突触后致密部(PSD)大小、棘头体积、棘头宽度和棘颈宽度较小。将棘突触分为五类表明,15q重复小鼠中蘑菇状棘的频率有降低趋势。这些结果表明,15q重复小鼠中形态不成熟的兴奋性突触相对增加,但星形胶质细胞接触更多,这可能与ASD小鼠模型中观察到的突触更新增强有关。

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