Growth and Development of the Striatum in Huntington's Disease

项目摘要 该提案是一项独特研究的竞争性更新，该研究测量了体积，功能和 亨廷顿病（HD）高危儿童纹状体的发育。HD是一种神经退行性疾病 一种由DNA三联体重复序列（CAG）扩增引起的疾病，表现为认知、行为和运动 变化平均发病年龄为40岁。这种疾病最终会影响大多数大脑区域，但主要的 病理位于纹状体。退化是疾病过程中的一个关键组成部分， 过去的几年支持了这样一种观点，即HD的病理学的一个重要组成部分是异常的 大脑发育该补助金于2009年获得资助，通过对处于风险中的儿童的研究来调查这一假设 父母为孝，父母为孝。由于HD是一种常染色体显性遗传疾病，每个孩子都有50%的机会 继承权对有风险的参与者进行基因分型，并对基因扩增（GE）的参与者进行比较 第三个对照组是健康对照儿童（HC）（在正常儿童中没有HD）。 家庭）。评估包括MRI和运动功能，认知技能和行为的测量。 目前的建议旨在通过对增长进行更彻底的评估来扩展我们的研究 和纹状体的发育。最初的研究使用结构磁共振评估体积 成像（sMRI）和使用扩散张量成像（DTI）的白色物质完整性。结果（显示为进行中 报告）表明纹状体体积不足，丘脑相对保留或扩大， 小脑;和异常分数各向异性（FA）在多个轨道。新方案将增加：1） 纹状体静息状态功能连接性MRI（fcMRI）的评价，2）纹状体静息状态功能连接性MRI（fcMRI）的分子测量， 完整性使用（1）H磁共振波谱（MRS），和3）发育的评价 通过“加速纵向”格式的大脑结构的轨迹（6-18岁之间的生长）。 补偿机制，如小脑和丘脑的过度生长也将进行研究。 功能评估将包括认知和运动技能的测量。由此获得的信息 这项建议可能是确定神经保护干预措施的最早可能时间框架的关键。

PROJECT SUMMARY This proposal is a competitive renewal for a unique study that measures the volume, function, and development of the striatum in children at risk for Huntington's Disease (HD). HD is a neurodegenerative disease caused by a DNA triplet repeat (CAG) expansion and manifests in cognitive, behavioral, and motor changes. Average age of onset is 40 yrs. The disease eventually affects most brain regions, yet the primary pathology is located in the striatum. Degeneration is a key component in the disease process, yet research in the past few years has supported the notion that a crucial component of the pathoetiology of HD is abnormal brain development. The grant was funded in 2009 to investigate this hypothesis by the study of children at risk for HD (those with a parent with HD). As HD is an autosomal dominant disease, each child has a 50% chance of inheritance. The at-risk participants are genotyped and those who are gene-expanded (GE) are compared to those who are gene non-expanded (GNE); a 3rd comparison group is healthy control children (HC) (no HD in family). Assessments include MRI and measures of motor function, cognitive skills, and behavior. The current proposal is designed to extend our studies by conducting a more thorough evaluation of the growth and development of the striatum. The original study evaluated volumes using structural Magnetic Resonance Imaging (sMRI) and white matter integrity using Diffusion Tensor Imaging (DTI). Results (shown in progress report) indicate volume deficits in the striatum with relative sparing or enlargement of the thalamus and cerebellum; and abnormal fractional anisotropy (FA) in multiple tracks. The new protocol will add: 1) evaluation of striatal resting state functional connectivity MRI (fcMRI), 2) Molecular measures of striatal integrity using (1)H magnetic resonance spectroscopy (MRS), and 3) the evaluation of developmental trajectories (growth between ages 6-18 years) of brain structure via an 'accelerated longitudinal' format. Compensatory mechanisms such as overgrowth of the cerebellum and thalamus will also be investigated. Functional assessment will include measures of cognition and motor skill. Information gained from this proposal could be key to identifying the earliest possible time-frame for neuroprotective interventions.