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

从斑马鱼到患者：利用斑马鱼揭示神经发育障碍中攻击行为的遗传和神经基础

• 批准号: 2749412
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749412
• 关键词: zebrafish; patients; Using; uncover; genetic

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

自闭症谱系障碍(ASD)是一种普遍存在的神经发育疾病，以重复行为和社交困难为特征。这是一种非常复杂的疾病，据了解，发生这种疾病的原因是环境和遗传因素共同影响突触。据报道，25%的自闭症病例被归因于遗传影响。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都有不利影响。对于患有自闭症的儿童来说，攻击性行为与社会关系中的不利后果有关，例如成为受害者的风险或需要身体干预，以及被安置在限制性环境中。对自闭症患者的照顾者也有不利的后果，较高的压力水平、缺乏支持和经济压力对日常生活产生负面影响。尽管全球自闭症发病率上升，攻击性是自闭症患者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。这是因为我们对这些突变如何扰乱大脑的发育轨迹和连接的潜在机制缺乏了解。通过将现有的小鼠数据与本文概述的斑马鱼研究相结合，将被用于解决以下问题：NRXN1基因敲除和Nlgn3A451C突变对挑战行为(攻击/焦虑)的影响轴突生长/突触形成E/I平衡利用斑马鱼突变体进行新化合物的药理学筛选，可能改善与ASD相关的攻击行为