Yang Jian-Quan, Yin Bao-Qi, Yang Chao-Hua, Jiang Miao-Miao, Li Zhe
Department of Children's Rehabilitation, Research Center of Rehabilitation Medicine in Henan, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Front Neurosci. 2025 Jan 17;18:1467047. doi: 10.3389/fnins.2024.1467047. eCollection 2024.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and the presence of restrictive and repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Recent studies have indicated that early rehabilitative intervention can alleviate the symptoms of individuals with ASD. However, there remain unsolved issues of behavioral intervention such as the appropriate time and types of therapies. In this study, we employed a mouse model prenatally exposed to valproic acid to establish a validated ASD mouse model and We found that paired-housing with control mice for 4 week after weaning palliated sociability deficits, anxiety and repetitive behaviors in this model of ASD-like behaviors, while paired-housing with their ASD littermate did not produce this effects. Furthermore, by evaluating different time window of paired-housing, we found that paired-housing during postnatal day 21 (P21) to P35, but not P21 to P28 or P35 to P49 or P28 to P35, is a critical period for the influence of paired-housing on autistic-like behaviors. Finally, paired-housing with control mice improved the impaired GABA system in this model of ASD. So our study demonstrates the therapeutic potential of environmental intervention during a critical period in the treatment of ASD.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交沟通受损以及存在限制性和重复性的行为。由于与该疾病相关的众多风险因素和复杂症状，研究病因过程并确定合适的治疗靶点仍然是克服ASD的艰巨挑战。最近的研究表明，早期康复干预可以缓解ASD患者的症状。然而，行为干预仍存在一些未解决的问题，例如合适的治疗时间和治疗类型。在本研究中，我们使用了产前暴露于丙戊酸的小鼠模型来建立一个经过验证的ASD小鼠模型，并且我们发现，断奶后与对照小鼠配对饲养4周可减轻该ASD样行为模型中的社交缺陷、焦虑和重复行为，而与其ASD同窝小鼠配对饲养则不会产生这种效果。此外，通过评估配对饲养的不同时间窗口，我们发现出生后第21天（P21）至P35天期间的配对饲养，而非P21至P28天、P35至P49天或P28至P35天，是配对饲养对自闭症样行为产生影响的关键时期。最后，与对照小鼠配对饲养改善了该ASD模型中受损的GABA系统。因此，我们的研究证明了关键时期环境干预在ASD治疗中的潜在治疗作用。
