Cortical neurotransmitters dynamics in the Rasopathies

Rasopathies 中的皮质神经递质动力学

• 批准号: 2898105
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2898105
• 关键词: Cortical; neurotransmitters; dynamics; Rasopathies

Rasopathies such as Neurofibromatosis 1 (NF1) and Noonan syndrome (NS) are a group of rare genetic disorders that affect 1 in 1000 people. Much of the real-life impact of NF1/NS on children relates to learning and behavioural difficulties with long-term consequences on academic/occupational functioning. Problems with 'working memory' (WM) are particularly relevant for day-to-day functioning for listening to /remembering short-term information, following instructions, reasoning, and making decisions. Currently, there are no effective treatments for these difficulties. The aim of this doctoral study is to understand how brain push-pull neurotransmitters Glutamate and GABA fluctuate during learning. Research conducted in animal models of NF1/NS suggest that these neurotransmitters may underlie learning problems, but these mechanisms have not been investigated in humans. To achieve our aim, the study will recruit 30 children each with NF1, NS and healthy controls to the study. The student will use novel MRI methods called functional magnetic spectroscopy to quantify the ratio of Glutamate/GABA neurotransmitters at rest and the glutamate released in the brain during performance of a learning task. The study will investigate how the brain mechanisms in NF1/NS groups are different from controls. Understanding these mechanisms is important to allow design of appropriate interventions - for example non-invasive brain stimulation which can be used to modulate neuroplasticity. The project will be embedded within a wider project funded by NIHR Biomedical Research Centre and will benefit from access to administrative support and funding. The student will receive training in the design of functional MR experiments, clinical research skills, learning how to collect and analyze neuroimaging data. There is expertise within the supervisory team in psychiatry, cognitive neuroscience, computational modelling and neuroradiology. The supervisory team have a track record of scanning children with neurodevelopmental disorders.

神经纤维瘤病（NF1）和努南综合征（NS）等rasopathy是一组罕见的遗传性疾病，每1000人中就有1人患病。NF1/NS对儿童的现实影响主要涉及学习和行为困难，并对学业/职业功能产生长期影响。“工作记忆”（WM）的问题与倾听/记忆短期信息、遵循指示、推理和做决定等日常功能特别相关。目前，这些困难没有有效的治疗方法。这项博士研究的目的是了解大脑推拉神经递质谷氨酸和GABA在学习过程中如何波动。在NF1/NS动物模型中进行的研究表明，这些神经递质可能是学习问题的基础，但这些机制尚未在人类中进行研究。为了达到我们的目的，本研究将招募30名患有NF1、NS和健康对照的儿童参与研究。该学生将使用一种称为功能磁波谱的新型MRI方法来量化休息时谷氨酸/GABA神经递质的比例，以及学习任务期间大脑中释放的谷氨酸的比例。该研究将调查NF1/NS组的大脑机制与对照组有何不同。了解这些机制对于设计适当的干预措施非常重要，例如可以用来调节神经可塑性的非侵入性脑刺激。该项目将被纳入国家卫生研究院生物医学研究中心资助的一个更广泛的项目，并将受益于获得行政支持和资助。学生将接受功能磁共振实验设计、临床研究技能、神经影像数据收集和分析等方面的培训。监督团队中有精神病学、认知神经科学、计算建模和神经放射学方面的专业知识。监督小组有扫描患有神经发育障碍的儿童的记录。