Petrinovic Marija M, Künnecke Basil
F. Hoffmann-La Roche AG, pRED, Pharma Research and Early Development, DTA Neuroscience, Building 68, Room 327A, Grenzacherstrasse 124, 4070, Basel, Switzerland.
Psychopharmacology (Berl). 2014 Mar;231(6):1167-89. doi: 10.1007/s00213-013-3200-z. Epub 2013 Jul 14.
Autism spectrum disorder(s) (ASDs) is a neurodevelopmental disorder characterized by stereotyped behaviours and impairments in communication and social interactions. This heterogeneity has been a major obstacle in uncovering the aetiology and biomarkers of ASDs. Rodent models with genetic modifications or environmental insults have been created to study particular endophenotypes and bridge the gap between genetics and behavioural phenotypes. Translational neuroimaging modalities with their ability to screen the brain noninvasively and yield structural, biochemical and functional information provide a unique platform for discovery and evaluation of such endophenotypes in preclinical and clinical research.
We reviewed literature on translational neuroimaging in rodent models of ASDs. The most prominent models will be described and the respective neuroimaging endophenotypes will be discussed with reference to human data. A perspective on future directions of translational neuroimaging in animal models of ASDs will be given.
To date, we experience a proliferation of rodent models which recapitulate specific liabilities identified in ASDs patients. Translational neuroimaging in these models is emerging but is skewed towards magnetic resonance imaging (MRI) modalities. Volumetric and structural assessments of the brain are dominating and a host of endophenotypes have been reported that allude to findings in ASDs patients but with only few to converge among the models. Caveats of current studies are the diverging biological conditions related to genetic background and age of the animals. It is anticipated that longitudinal and functional assessments will gain much importance and will help elucidating mechanistic relationship between behavioural and structural endophenotypes.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征为刻板行为以及沟通和社交互动障碍。这种异质性一直是揭示ASD病因和生物标志物的主要障碍。人们已创建了具有基因修饰或环境损伤的啮齿动物模型，以研究特定的内表型，并弥合遗传学与行为表型之间的差距。具有无创筛查大脑并提供结构、生化和功能信息能力的转化神经成像方法，为在临床前和临床研究中发现和评估此类内表型提供了一个独特的平台。
我们回顾了关于ASD啮齿动物模型转化神经成像的文献。将描述最突出的模型，并参照人类数据讨论各自的神经成像内表型。将给出关于ASD动物模型转化神经成像未来方向的展望。
迄今为止，我们看到了大量的啮齿动物模型，这些模型概括了在ASD患者中发现的特定缺陷。这些模型中的转化神经成像正在兴起，但偏向于磁共振成像（MRI）方法。大脑的体积和结构评估占主导地位，并且已经报道了许多内表型，这些内表型暗示了在ASD患者中的发现，但各模型之间只有少数趋同。当前研究的注意事项是与动物遗传背景和年龄相关的不同生物学条件。预计纵向和功能评估将变得更加重要，并将有助于阐明行为和结构内表型之间的机制关系。
