Pal Akansha, Goel Falguni, Garg Vipin Kumar
Department of Pharmaceutical Technology, Meerut Institute of Engineering & Technology (MIET), Meerut, India.
Neurogenetics. 2025 Jun 6;26(1):48. doi: 10.1007/s10048-025-00828-5.
Autism Spectrum Disorder, a complex neurodevelopmental disorder, is manifested by deficits in social communication and restricted, repetitive patterns of behavior, interests, or activities. Its molecular mechanism of pathology is not that much understood, though various genetic mutations have been established in its causation. The most important genes are Shank3, Cntnap2, Neuroligin3, and Arid1b. Recently, zebrafish (Danio rerio) have emerged as a highly valuable model organism to study these genetic contributions to ASD, given their genetic tractability, transparent embryos, and ease of behavioral assessment. This review discusses the models of zebrafish used to examine the roles of Shank3, Cntnap2, Neuroligin3, and Arid1b in synaptic function, neuronal connectivity, and behavioral abnormalities characteristic of ASD. We discuss the molecular pathways affected by mutations in these genes, including synapse formation, excitatory/inhibitory balance, and neuronal signaling, which lead to the neurodevelopmental impairments observed in ASD. We have also highlighted the various behavioral assays in zebrafish, such as social interaction tests, sensory processing assays, and repetitive behavior measurements, which are used to study ASD-like phenotypes. The unique advantages of zebrafish include high-throughput potential, the ability to monitor real-time neuronal activity, and the ease with which genetic manipulations can be done. The review focuses on the advancement of zebrafish in understanding ASD and their potential for rising targeted interventions to address core symptoms of the disorder.
自闭症谱系障碍是一种复杂的神经发育障碍，表现为社交沟通缺陷以及行为、兴趣或活动的受限和重复模式。尽管已确定其病因中有多种基因突变，但其分子病理机制尚未得到充分了解。最重要的基因是Shank3、Cntnap2、Neuroligin3和Arid1b。最近，斑马鱼（Danio rerio）已成为研究这些基因对自闭症谱系障碍影响的极有价值的模式生物，因为它们具有遗传易处理性、胚胎透明且易于进行行为评估。本综述讨论了用于研究Shank3、Cntnap2、Neuroligin3和Arid1b在自闭症谱系障碍特征性的突触功能、神经元连接和行为异常中作用的斑马鱼模型。我们讨论了这些基因的突变所影响的分子途径，包括突触形成、兴奋性/抑制性平衡和神经元信号传导，这些途径导致了自闭症谱系障碍中观察到的神经发育障碍。我们还强调了斑马鱼中的各种行为测定方法，如社交互动测试、感觉处理测定和重复行为测量，这些方法用于研究自闭症谱系障碍样表型。斑马鱼的独特优势包括高通量潜力、监测实时神经元活动的能力以及易于进行基因操作。本综述重点关注斑马鱼在理解自闭症谱系障碍方面的进展及其为解决该疾病核心症状而开展靶向干预的潜力。
