Characterising a newly-identified modulator of ADHD risk: the behavioural and neural functions of steroid sulfatase

表征新发现的 ADHD 风险调节剂：类固醇硫酸酯酶的行为和神经功能

• 批准号: G0900636/1
• 负责人: William Davies
• 金额: $ 54.8万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900636%2F1
• 关键词: Characterising; newly; identified; modulator; ADHD

Children with Attention Deficit Hyperactivity Disorder (or ADHD as it is more commonly known) have trouble concentrating, are hyperactive and often act without giving due thought to the consequences of their actions. Moreover, they are often anxious, aggressive and have problems sleeping. Consequently, they often have difficulties regarding education and social interactions, which can cause substantial and deleterious knock-on effects on their adult lives.Many studies have shown that ADHD risk has a strong genetic basis. Interestingly, ADHD seems to affect boys far more commonly than girls, implying that one or more genes on the X or Y chromosomes may influence vulnerability to developing the disorder. Recent work in mice and in humans has identified one gene on the X chromosome which may influence this vulnerability. The gene is called STS, and when it is absent boys (or mice) are prone to developing symptoms associated with ADHD. The protein made by the STS gene is called steroid sulfatase. Currently, little is known about the role steroid sulfatase plays in the brain, and in particular, how it might act to influence attention and impulsivity. As experiments on human brain function are difficult to perform and limited in their scope, the present proposal will use mice to identify the effects of steroid sulfatase manipulation on brain development and function, with a view to characterising the function of the protein. These experiments should give us important clues as to what is going wrong in the brains of subjects with ADHD, an essential first step to working out how we might remedy it. The results obtained from our studies might also ultimately help us to develop therapies against other common and debilitating disorders associated with attention and impulsivity problems, including autism and schizophrenia.

患有注意力缺陷多动障碍（或更常见的ADHD）的儿童难以集中注意力，过度活跃，并且经常不适当考虑其行为的后果。此外，他们经常焦虑，好斗，睡眠有问题。因此，他们往往在教育和社会交往方面遇到困难，这可能会对他们的成年生活造成重大和有害的连锁反应。许多研究表明，ADHD风险具有很强的遗传基础。有趣的是，ADHD对男孩的影响似乎比女孩更普遍，这意味着X或Y染色体上的一个或多个基因可能会影响发展这种疾病的脆弱性。最近在小鼠和人类中的研究已经确定了X染色体上的一个基因可能会影响这种脆弱性。这种基因被称为STS，当它缺失时，男孩（或小鼠）容易出现与ADHD相关的症状。由STS基因产生的蛋白质被称为类固醇硫酸酯酶。目前，人们对类固醇硫酸酯酶在大脑中的作用知之甚少，特别是它如何影响注意力和冲动。由于人脑功能的实验难以进行，而且范围有限，本提案将使用小鼠来确定类固醇硫酸酯酶操作对大脑发育和功能的影响，以期表征蛋白质的功能。这些实验应该能为我们提供重要的线索，让我们了解ADHD受试者的大脑到底出了什么问题，这是我们找到治疗方法的重要第一步。我们的研究结果可能最终会帮助我们开发出治疗其他常见的、与注意力和冲动问题相关的衰弱性疾病的疗法，包括自闭症和精神分裂症。