Abstract:
Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.
摘要:
自闭症谱系障碍(ASD)是一组神经发育障碍,其特征是社交互动和交流不足,重复或刻板的行为。自闭症儿童更容易出现视力问题,ASD在盲人中异常常见。然而,自闭症视力障碍背后的机制尚不清楚。在胚胎发育过程中通过XAV939稳定WNT靶向支架蛋白Axin2会导致皮质神经元过度产生,并导致小鼠自闭症样行为。在这项研究中,我们使用XAV939诱导的自闭症小鼠模型研究了视力异常与自闭症之间的关系.我们发现接受XAV939的小鼠具有降低的强光适应性ERG的幅度。从XAV939处理的小鼠记录的闪光视觉诱发电位的幅度和潜伏期更低和更长,分别比对照小鼠,表明XAV939抑制视觉信号处理和电导。解剖学上,当Axin2在发育过程中稳定时,RGC轴突的直径减小,视神经纤维的髓鞘有缺陷,少突胶质细胞减少。结果表明,WNT信号通路对视神经发育至关重要。这项研究提供了实验证据,表明干扰大脑发育的条件也可能导致视觉问题,这反过来可能会夸大人类的自闭症特征。