From zebrafish to patients: Using zebrafish to uncover the genetic and neural basis of aggression in neurodevelopmental disorders

自闭症谱系障碍（ASD）是一种普遍的神经发育状况，其特征是重复行为和社交困难。这是一种非常复杂的疾病，据了解是由于环境和遗传因素影响突触的组合而发生的。据报道，25%的ASD病例归因于遗传影响。三分之二的自闭症患者表现出更强的攻击性，对受影响的个人及其家庭的生活质量产生不利影响。对于患有ASD的儿童，攻击行为与社会关系中的不良结果有关，例如被剥夺或需要身体干预的风险以及在限制性环境中的安置。对于ASD患者的照顾者来说，也有不利的结果，对日常生活产生负面影响，因为压力水平较高，缺乏支持和经济压力。尽管自闭症的发病率在全球范围内增加，并且攻击性是自闭症患者的照顾者面临的最大挑战之一，但我们缺乏有效的治疗方法。现有的治疗方法借鉴了其他神经精神疾病的成功治疗方法。这是因为我们对这些突变如何扰乱发育轨迹和大脑布线的潜在机制缺乏了解。通过结合现有的小鼠数据和本文概述的斑马鱼研究，将用于解决以下问题：NRXN 1敲除和Nlgn 3A 451 C突变对以下方面的影响：挑战性行为（攻击/焦虑）轴突生长/突触形成E/I平衡全脑活动使用斑马鱼突变体用于药理学筛选可能改善ASD相关攻击行为的新型化合物

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by repetitive behaviours and difficulties in social interaction. It is a very complex disorder, understood to occur due to a combination of environmental and genetic factors affecting synapses. 25% of ASD cases have been reported to be attributed to genetic influence. 2-out-of-3 autistic individuals show increased aggression, having detrimental effects on the quality of life of both affected individuals and their families. For children with ASD, aggressive behaviour is associated with adverse outcomes in social relationships, such as the risk of being victimised or physical intervention required and placement in restrictive settings. There are also adverse outcomes for caregivers of individuals with ASD, with negative impacts on day-to-day life from higher stress levels, lack of support and financial strain. Despite the worldwide incidence increase of autism, and aggression being one of the most reported challenges faced by caregivers of autistic individuals, we lack effective treatments. Available treatments have borrowed from successful treatment of other neuropsychiatric disorders. This is because of our poor understanding of underlying mechanisms of how these mutations perturb developmental trajectories and wiring of the brain. by combining existing mouse data with the zebrafish studies outlined here, will be employed to address the following: The impact of NRXN1 knockout and Nlgn3A451C mutation on: challenging behaviours (aggression/anxiety) axonal growth/synapse formation E/I balance whole brain activity Use of zebrafish mutants for pharmacological screening of novel compounds which may improve ASD-associated aggressive behaviour