Pathogenesis Of Essential Tremor: Cerebellar Metabolism

特发性震颤的发病机制：小脑代谢

• 批准号: 7277644
• 负责人: ELAN D LOUIS
• 金额: $ 46.04万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277644
• 关键词: Address; Age; Aging; Animal Model; Animals; Antibodies; Asia; Autopsy; Axon; Basal Ganglia; Biochemical; Biology; Brain; Brain region; Butyric Acid; Butyric Acids; Canada; Carrier Proteins; Cells; Cerebellar vermis structure; Cerebellum; Cessation of life; Characteristics; Cities; Clinical; Clinical Research; Collection; Condition; Deep Brain Stimulation; Development; Disease; Dopamine Agonists; Dose; Essential Tremor; Family history of; First Degree Relative; Foundations; Frequencies; Gender; General Population; Gliosis; Globus Pallidus; Glutamate Decarboxylase; Glutamates; Goals; Golgi Apparatus; Head; Image; Individual; Inferior; International; Kansas; Knowledge; Label; Lead; Levodopa; Location; Medical center; Medulla oblongata olive; Metabolic Pathway; Metabolism; Methods; Motor Cortex; Neuroglia; Neurons; Neurotransmitters; New York; Numbers; Parkinson Disease; Pathogenesis; Pathology; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Presbyterian Church; Publishing; Purkinje Cells; Race; Red nucleus structure; Research; Research Personnel; Severities; Source; Staining method; Stains; Structure; Substantia nigra structure; Swelling; System; Thalamic structure; Time; Tissues; Torpedo; Transaminases; Tremor; United States; Universities; University Hospitals; Upper arm; astrogliosis; base; brain tissue; cell injury; cell type; clinical Diagnosis; design; illness length; interest; mind control; nervous system disorder; neurochemistry; neuroimaging; neurotransmission; prospective; putamen; repository; response; response to injury; white matter

DESCRIPTION (provided by applicant): Essential tremor (ET) is the most common tremor disorder, twenty times more prevalent than Parkinson's disease. Up to 6% of the general population has ET. Uncontrollable trembling eventually forces 10 - 25% of patients to retire prematurely. There is no cure, and few medications lessen the tremor, although deep brain stimulation has provided promising results. Clinical evidence and neuro-imaging studies suggest that the cerebellum is centrally involved in ET, and evidence from clinical and animal studies suggests that there may be a disturbance in the gamma amino butyric acid (GABA) neurotransmitter system. While ET is clinically progressive, little is known about its underlying pathology. There have been few published postmortem examinations. The fundamental question in ET research is whether an underlying pathology can be identified in terms of morphological or morphometric changes of specific cell types in specific brain regions? Second, is there a neurotransmitter abnormality in ET, either resulting as a consequence of cell loss or in the absence of cell loss? The proposed study will be a collaborative effort involving four centers in the United States and Canada where archival postmortem tissue on 24 ET patients is available. In addition, with the help of the International Essential Tremor Foundation, we will establish at Columbia University a centralized repository for new prospectively-collected ET brains, collecting 36 additional ET brains during the five-year period. The 60 ET brains will be compared with 40 control brains. Primary Aim 1 is to study the pathology of ET to determine whether there are changes in specific brain regions. Using conventional morphological methods and quantitative morphometric assessments (stereology), tissue will be examined for changes, including cell loss, in the main region of interest (cerebellar hemispheres) and in secondary regions of interest (red nuclei, thalami, inferior olivary nuclei). We hypothesize that changes and cell loss in the cerebellum will be present to a greater extent in ET than in control brains. Primary Aim 2 is to study the GABA neurotransmitter system. We hypothesize that there will be differences in cerebellar GABA-ergic immuno-labeling in ET compared to control brains. Current therapies for ET have come to us by serendipity and are ineffective in up to 50% of patients. Knowledge of the pathological changes and neurochemical abnormality in ET is critical for the design of new therapies for ET.

描述(申请人提供)：特发性震颤(ET)是最常见的震颤障碍，比帕金森氏症的发病率高20倍。高达6%的总人口有ET。无法控制的颤抖最终会迫使10%-25%的患者提前退休。目前还没有治愈的方法，几乎没有药物可以减轻震颤，尽管深部脑刺激已经提供了令人振奋的结果。临床证据和神经影像研究表明，小脑参与了ET的中枢作用，临床和动物研究表明，GABA神经递质系统可能存在紊乱。虽然ET在临床上是进展性的，但对其潜在的病理机制知之甚少。很少有发表过的尸检报告。ET研究中的基本问题是，是否可以根据特定脑区特定细胞类型的形态或形态计量学变化来识别潜在的病理？第二，ET是否存在神经递质异常，无论是由于细胞丢失还是在没有细胞丢失的情况下？这项拟议的研究将是一项合作努力，涉及美国和加拿大的四个中心，那里有24名ET患者的尸检组织档案。此外，在国际基本震颤基金会的帮助下，我们将在哥伦比亚大学建立一个新的预期收集的ET大脑的中央储存库，在五年内额外收集36个ET大脑。60名外星人的大脑将与40名对照组的大脑进行比较。主要目的1是研究ET的病理，以确定是否有特定脑区的变化。使用常规的形态学方法和定量形态计量学评估(体视学)，将在主要感兴趣区(小脑半球)和次要感兴趣区(红核、丘脑、下橄榄核)检查组织的变化，包括细胞丢失。我们假设，与对照组相比，ET患者小脑中的变化和细胞丢失的程度更大。主要目的2是研究GABA神经递质系统。我们假设，与对照组相比，ET组的小脑GABA能免疫标记会有所不同。目前治疗ET的方法是偶然出现的，在高达50%的患者中无效。了解ET的病理变化和神经化学异常对于设计新的ET治疗方法至关重要。