Integrated multidisciplinary approach for analyzing diffuse myelination disorders

分析弥漫性髓鞘形成疾病的综合多学科方法

基本信息

批准号：
7740563
负责人：
MARGOT MAYER-PROSCHEL
金额：
$ 92.1万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-11 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7740563
关键词：
Acoustic Nerve Address Affect Alcoholism American Attention deficit hyperactivity disorder Auditory Auditory Brainstem Responses Auditory system Autistic Disorder Axon Behavioral Brain Brain Stem Cells Child Chronic Clinical Data Defect Demyelinations Development Diagnosis Diagnostic Diffuse Disease Early Diagnosis Electrons Exposure to Failure Functional disorder Generations Hearing Hypoxia Immunohistochemistry Impairment Inflammatory Injury Intervention Iron Magnetic Resonance Imaging Maintenance Malnutrition Measurement Mental Depression Metabolic Methods Microscopic Modeling Monitor Mothers Myelin Nerve Nervous System Trauma Neural Conduction Neuraxis Population Pregnancy Process Psychotic Disorders Research Response Latencies Schizophrenia Symptoms Syndrome Systems Analysis Testing Therapeutic Therapeutic Intervention Time Toxic Environmental Substances Virus Diseases Work base chemotherapeutic agent clinically relevant design in vivo interdisciplinary approach longitudinal analysis myelination novel diagnostics novel strategies offspring prevent research study response social skills therapy design tool

项目摘要

Diffuse demyelination disorders affect more than one-quarter million of Americans and are associated with a wide range of clinical manifestations. They can occur due to chronic alcoholism and malnourishment, inflammatory processes, viral infection, hypoxic-ischemic injury, focal depression, metabolic dysfunction and as we show in our own work, by exposure to environmental toxicants and chemotherapeutic agents. Another class of diseases that are distinct from demyelination are those in which there is a failure to form myelin, resulting in hypomyelination. A large number of hypomyelinations are a consequence of insults to the developing brain and most frequently occur in children. Hypomyelination is often associated with lower IQ, delayed or impaired verbal skills and social and behavioral abnormalities and has been described to be associated with autism, attention deficit/hyperactivity disorder, psychosis and schizophrenia. The diagnostic study of demyelinating and hypomyelinating disorders is severely hampered by the difficulty to diagnose such diseases prior to the onset of severe clinical symptoms, as current diagnostic tools such as magnetic resonance imaging or histopathological analysis are either limited in their sensitivity and costly, or require invasive methods, that generate only confirmatory results. We propose to provide the basis for the development of a new approach that allows the early diagnosis and intervention for de- and hypomyelinating disorders using the highly sensitive auditory system as a functional readout. We will characterize the impact of mechanism by which target cells in the auditory system respond to the insults and use this new approach to determine the efficacy of therapeutic interventions that are designed to restore auditory nerve conduction specifically and proper myelination in the brain in general.

弥漫性脱髓鞘疾病影响了超过四分之一的美国人，并且与广泛的临床表现有关。它们可能由于慢性酒精中毒和营养不良，炎症过程，病毒感染，缺氧 - 缺血性损伤，局灶性抑郁症，代谢功能障碍以及我们在自己的工作中所显示的，通过接触环境有毒物质和化学治疗剂。另一种与脱髓鞘不同的疾病是那些未能形成髓磷脂的疾病，导致低切髓。大量的低触及递减是对发展中大脑的侮辱，并且最常发生在儿童中。低切术通常与智商较低，延迟或降低的言语技能以及社会和行为异常有关，并被描述为与自闭症，注意力缺陷/多动障碍，精神病和精神分裂症有关。在严重的临床症状发作之前难以诊断此类疾病的困难，因为当前的诊断工具（例如磁共振成像或组织病理学分析）的敏感性和成本较高，或者需要侵入性的确认结果，因此，仅限制了磁共振成像或组织病理学分析，从而严重阻碍了脱髓鞘和脱髓性疾病的诊断研究严重阻碍了这种疾病。我们建议为开发一种新方法提供基础，该方法允许使用高度敏感的听觉系统作为功能读数进行早期诊断和干预，以降低和降低疾病。我们将表征听觉系统中的靶细胞对侮辱的反应的机制的影响，并使用这种新方法来确定旨在恢复大脑中专门恢复听觉神经传导的治疗干预措施的功效。