PDF(Pubmed)
Abstract：
Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.
摘要：
受限,重复行为是包括自闭症谱系障碍在内的神经发育障碍的常见症状。尽管与不良的发育结果有关，对重复行为的了解仍然很少，并且治疗选择有限。环境富集削弱了重复行为的发展，但确切的机制仍然不清楚。使用重复行为的C58小鼠模型，我们进行了扩散张量成像，以检查与重复行为的发展相关的微观结构变化及其通过环境富集的衰减。C57BL/6小鼠品系，显示很少或没有重复行为，作为对照组。我们观察到C58小鼠和C57BL/6小鼠之间扩散指标的广泛差异。在幼年C58小鼠中，重复运动行为与多个灰质区域的分数各向异性表现出强负相关，而在年轻的成年C58小鼠中，高重复运动行为与纹状体中较低的分数各向异性和较高的径向扩散率密切相关。环境富集增加了C58幼年小鼠大脑中整个灰质区域的分数各向异性和轴向扩散率，并且主要与与重复行为相关的小脑和感觉区域重叠。我们的结果表明，环境富集通过改变小脑中的灰质微观结构来减少重复行为的发展，内侧内嗅皮层，和幼年C58小鼠的感觉处理区域。在标准实验室条件下，在成年C58小鼠中,这些区域的早期病理似乎导致了后来的纹状体和白质功能障碍.未来的研究应检查这些区域在重复行为发展中的作用以及感觉加工与小脑缺陷和重复行为之间的关系。
