Growth and Development of the Striatum in Huntington's Disease

亨廷顿病纹状体的生长和发育

• 批准号: 8719183
• 负责人: PEGGY C NOPOULOS
• 金额: $ 58.92万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719183
• 关键词: Affect; Age; Age of Onset; Anisotropy; Behavior; Behavioral; Brain; Brain region; Budgets; CAG repeat; Cerebellum; Child; Cognition; Cognitive; Corpus striatum structure; DNA; Development; Diffusion Magnetic Resonance Imaging; Disease; Evaluation; Family; Financial compensation; Funding; Genes; Genotype; Glutamates; Glutamine; Goals; Grant; Growth; Growth and Development function; Huntington Disease; Impulsivity; Insula of Reil; Intervention; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Memory; Metabolic; Molecular; Motor; Motor Skills; N-acetylaspartate; Neurodegenerative Disorders; Occipital lobe; Onset of illness; Parents; Parietal lobe gyrus; Participant; Pathology; Process; Progress Reports; Protocols documentation; Relative (related person); Research; Rest; Risk; Seeds; Structure; Thalamic structure; Time; Trinucleotide Repeats; base; brain volume; cognitive function; comparison group; design; frontal lobe; inattention; interest; molecular marker; public health relevance; putamen; skills; white matter

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本提案是一项独特研究的竞争性更新，该研究测量有亨廷顿病 (HD) 风险的儿童纹状体的体积、功能和发育。 HD 是一种由 DNA 三联体重复 (CAG) 扩增引起的神经退行性疾病，表现为认知、行为和运动变化。平均发病年龄为40岁。该疾病最终影响大多数大脑区域，但主要病理位于纹状体。退化是疾病过程中的一个关键组成部分，但过去几年的研究支持了这样的观点：HD 病理学的一个关键组成部分是大脑发育异常。该拨款于 2009 年资助，旨在通过对有 HD 风险的儿童（父母患有 HD 的儿童）进行研究来调查这一假设。由于HD是一种常染色体显性遗传疾病，每个孩子有50%的机会遗传。对有风险的参与者进行基因分型，并将基因扩展 (GE) 的参与者与基因非扩展 (GNE) 的参与者进行比较；第三比较组是健康对照儿童（HC）（家庭中没有HD）。评估包括 MRI 以及运动功能、认知技能和行为的测量。目前的提案旨在通过对纹状体的生长和发育进行更彻底的评估来扩展我们的研究。最初的研究使用结构磁共振成像 (sMRI) 评估体积，并使用扩散张量成像 (DTI) 评估白质完整性。结果（显示在进展报告中）表明纹状体体积不足，丘脑和小脑相对保留或增大；以及多个轨迹中的异常分数各向异性 (FA)。新协议将增加：1）评估纹状体静息状态功能连接性MRI（fcMRI），2）使用（1）H磁共振波谱（MRS）对纹状体完整性进行分子测量，3）通过“加速纵向”格式评估大脑结构的发育轨迹（6-18岁之间的生长）。还将研究小脑和丘脑过度生长等补偿机制。功能评估将包括认知和运动技能的测量。从该提案中获得的信息可能是确定神经保护干预措施的最早可能时间表的关键。