Chao Owen Y, Yunger Richelle, Yang Yi-Mei
Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA.
Swenson College of Science and Engineering, University of Minnesota Duluth, Duluth, MN, USA.
Behav Brain Res. 2018 Jul 16;347:140-147. doi: 10.1016/j.bbr.2018.03.014. Epub 2018 Mar 13.
Autism spectrum disorders (ASD) are diagnosed based on the behavioral criteria of impaired social interaction, defective communication and repetitive behaviors. Psychiatric comorbidities, such as anxiety and intellectual disability, are commonly present in ASD. The BTBR T+ Itpr3tf/J (BTBR) mice display a range of autistic phenotypes, yet whether this mouse model is appropriate to study psychiatric comorbidity in ASD remains unclear. We addressed this issue by subjecting the BTBR animals to three-chambered apparatus, open field, object attention test and elevated open platform. Compared to C57BL/6J control mice, the BTBR mice displayed hyperactivity in most of the tests. In the three-chamber assessment, they exhibited deficits in sociability. In the open field, more grooming and thigmotaxis and less rearing behaviors were observed. They also showed impaired object-based attention. On the elevated open platform, the BTBR animals stayed more to the edges than in the center of the platform. To further examine the properties of this test, naïve C57BL/6J mice were randomly administrated with saline or an anxiogenic substance, caffeine. The caffeine group demonstrated a similar behavioral pattern as the BTBR mice. When the saline group was re-exposed to the same platform, the time they stayed in the center substantially increased, likely due to reduced anxiety by habituation. These results indicate that the BTBR were more anxious than control mice on the open platform. Taken together, the BTBR strain exhibit emotional and cognitive impairments in addition to autistic behaviors, suggesting that they can be a valid model for ASD with psychiatric comorbidity.
自闭症谱系障碍（ASD）是根据社交互动受损、沟通缺陷和重复行为等行为标准来诊断的。精神共病，如焦虑和智力残疾，在ASD中很常见。BTBR T+ Itpr3tf/J（BTBR）小鼠表现出一系列自闭症表型，但这种小鼠模型是否适合研究ASD中的精神共病仍不清楚。我们通过将BTBR动物置于三室装置、旷场、物体注意力测试和高架开放平台来解决这个问题。与C57BL/6J对照小鼠相比，BTBR小鼠在大多数测试中表现出多动。在三室评估中，它们表现出社交能力缺陷。在旷场中，观察到更多的梳理行为和趋触性，以及更少的竖毛行为。它们还表现出基于物体的注意力受损。在高架开放平台上，BTBR动物更多地停留在平台边缘而不是中心。为了进一步研究该测试的特性，将未处理的C57BL/6J小鼠随机给予生理盐水或致焦虑物质咖啡因。咖啡因组表现出与BTBR小鼠相似的行为模式。当生理盐水组再次暴露于同一平台时，它们在中心停留的时间大幅增加，这可能是由于习惯化导致焦虑减少。这些结果表明，BTBR小鼠在开放平台上比对照小鼠更焦虑。综上所述，BTBR品系除了自闭症行为外还表现出情绪和认知障碍，这表明它们可以成为伴有精神共病的ASD的有效模型。
