Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
Neurology Department, Ulm University, Ulm, Germany.
Front Neural Circuits. 2019 Feb 22;13:6. doi: 10.3389/fncir.2019.00006. eCollection 2019.
Research efforts over the past decades have unraveled both genetic and environmental factors, which contribute to the development of autism spectrum disorders (ASD). It is, to date, largely unknown how different underlying causes result in a common phenotype. However, the individual course of development and the different comorbidities might reflect the heterogeneous genetic and non-genetic contributions. Therefore, it is reasonable to identify commonalities and differences in models of these disorders at the different hierarchical levels of brain function, including genetics/environment, cellular/synaptic functions, brain regions, connectivity, and behavior. To that end, we investigated transgenic mouse lines and compared them with a prenatal zinc-deficient (PZD) mouse model of ASD at the level of brain structural alterations in an 11,7 T small animal magnetic resonance imaging (MRI). Animals were measured at 4 and 9 weeks of age. We identified a decreased total brain volume (TBV) and hippocampal size of mice but a convergent increase of basal ganglia (striatum and globus pallidus) in most mouse lines. Moreover, transgenic mice had smaller thalami, whereas PZD mice had this region enlarged. Intriguingly, heterozygous knockout mice mostly showed minor abnormalities to full knockouts, which might reflect the importance of proper dosage in neuronal cells. Most reported volume changes seemed to be more pronounced at younger age. Our results indicate both convergent and divergent brain region abnormalities in genetic and non-genetic models of ASD. These alterations of brain structures might be mirrored in the reported behavior of both models, which have not been assessed in this study.
在过去的几十年里，研究人员已经揭示了导致自闭症谱系障碍 (ASD) 发展的遗传和环境因素。迄今为止，人们还不完全清楚不同的潜在原因如何导致共同的表型。然而，个体的发展过程和不同的合并症可能反映了遗传和非遗传因素的异质性。因此，在包括遗传学/环境、细胞/突触功能、脑区、连接和行为在内的大脑功能的不同层次上，识别这些疾病模型的共性和差异是合理的。为此，我们研究了转基因小鼠品系，并在 11.7T 小动物磁共振成像 (MRI) 水平上，将其与 ASD 的产前缺锌 (PZD) 小鼠模型进行了比较。在 4 周和 9 周大时对动物进行了测量。我们发现， 小鼠的总脑体积 (TBV) 和海马体大小减小，但大多数小鼠品系的基底节（纹状体和苍白球）体积增加。此外， 转基因小鼠的丘脑较小，而 PZD 小鼠的丘脑较大。有趣的是，杂合子敲除小鼠的异常情况比纯合子敲除小鼠少，这可能反映了神经元细胞中适当剂量的重要性。大多数报告的体积变化在年幼时似乎更为明显。我们的研究结果表明，遗传和非遗传 ASD 模型中都存在大脑区域的趋同和发散性异常。这些大脑结构的改变可能反映在两个模型的报告行为中，但在本研究中未进行评估。
