Longitudinal Diffusion Tensor Imaging Revealed Nerve Fiber Alterations in Aspm Mutated Microcephaly Model Mice
Longitudinal Diffusion Tensor Imaging Revealed Nerve Fiber Alterations in Aspm Mutated Microcephaly Model Mice
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DOI：
10.1016/j.neuroscience.2017.12.012
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发表时间：
2018-02
期刊：
影响因子：
3.3
通讯作者：
H. Ogi;Nobuhiro Nitta;So Tando;A. Fujimori;I. Aoki;S. Fushiki;K. Itoh
中科院分区：
文献类型：
--
作者：
H. Ogi;Nobuhiro Nitta;So Tando;A. Fujimori;I. Aoki;S. Fushiki;K. Itoh
常染色体隐性遗传性原发性小头畸形-5（MCPH 5）是由异常纺锤体样小头畸形相关（ASPM）基因突变引起的先天性小头畸形。本研究旨在证明放射学和病理学分析在评估出生后脑发育中的相关性，使用MCPH 5模型小鼠，ASP Mortholog（Aspm）敲除（KO）小鼠，在两个时间点（出生后3周; P3 W和P10 W）进行体内MRI，并在P5 W和P13 W进行补充的脑组织病理学分析。在MRI分析中，AspmKO小鼠在两个时间点均显示脑大小显著减小（平均差异8.6%），脑室较大（平均差异136.4%）。基于体素的统计显示，AspmKO小鼠在两个时间点的皮质和白色物质中的各向异性分数（FA）值均显著较低。与对照组相比，AspmKO小鼠FA值的发育变化不太显著。组织学分析显示，皮质层IV、V和VI中水平与垂直神经突的比率显著较高，对照小鼠在P13 W时根据成熟度显著增加（对照和KO之间的平均差异为12.7%），而KO小鼠在P13 W时VI层中的比率降低。AspmKO小鼠在P5 W时白色物质中髓鞘碱性蛋白阳性率显著降低。这些结果表明，时间FA的变化与病理结果密切相关，如异常的神经突生长和分化，这可能适用于分析患病的人脑发育。
Autosomal recessive primary microcephaly-5 (MCPH5) is characterized by congenital microcephaly and is caused by the mutation in the abnormal spindle-like, microcephaly-associated (ASPM) gene. This study aimed to demonstrate a correlation between radiological and pathological analyses in evaluating postnatal brain development using MCPH5-model mice,ASPMortholog (Aspm) knockout (KO) mice.In vivoMRI was performed at two time points (postnatal 3 weeks; P3W and P10W) and complementary histopathological analyses of brains were done at P5W and P13W. In the MRI analysis,AspmKO mice showed significantly decreased brain sizes (average 8.6% difference) with larger ventricles (average 136.4% difference) at both time points. Voxel-based statistics showed that the fractional anisotropy (FA) values were significantly lower inAspmKO mice in both the cortex and white matter at both time points. Developmental changes in the FA values were less remarkable in theAspmKO mice, compared with the controls. Histometric analyses revealed that the ratios of the horizontal to the vertical neurites were significantly higher in cortical layers IV, V and VI, with a remarkable increase according to maturation at P13W in the control mice (average 12.7% difference between control and KO), whereas the ratio in layer VI decreased at P13W in the KO mice. The myelin basic protein positive ratio in the white matter significantly decreased inAspmKO mice at P5W. These results suggest that temporal FA changes are closely correlated with pathological findings such as abnormal neurite outgrowth and differentiation, which may be applicable for analyzing diseased human brain development.