N-3 Fatty Acids: Roles in Parkinson's Disease

N-3 脂肪酸：在帕金森病中的作用

• 批准号: 7988494
• 负责人: BETH LEVANT
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7988494
• 关键词: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Abbreviations; Address; Affect; Age; Age-Years; American; Analytical Chemistry; Apoptosis; Apoptotic; Behavior; Behavioral; Brain; Bromodeoxyuridine; Cell Count; Cells; Clinical Research; Conceptions; Data; Development; Diet; Disease; Docosahexaenoic Acids; Dopamine; Dopaminergic Cell; Eicosanoids; Elderly; Future; GDNF gene; General Population; Goals; Individual; Interdisciplinary Study; Lead; Lesion; Lipids; Longevity; Mediating; Modeling; Nerve Degeneration; Neuroanatomy; Neurobiology; Neurodegenerative Disorders; Neurons; Neuropharmacology; Neurotoxins; Omega-3 Fatty Acids; Outcome Study; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Pathology; Phospholipids; Polyunsaturated Fatty Acids; Process; RXR; Rattus; Relative (related person); Risk; Rodent; Role; Substantia nigra structure; Testing; Therapy Clinical Trials; Time; Tissues; Variant; adduct; base; cytotoxic; docosapentaenoic acid; dopaminergic neuron; feeding; glial cell-line derived neurotrophic factor; innovation; neurochemistry; neurogenesis; neuropsychiatry; neurotoxic; nigrostriatal system; novel; pars compacta; prevent; public health relevance; young adult

DESCRIPTION (provided by applicant): Individuals with fewer nigrostriatal dopamine neurons appear to have increased vulnerability to insults and neuropathological processes that lead to Parkinson's disease. We have shown that young adult rats raised from conception on a diet low in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) have decreased brain levels of the n-3 PUFA docosahexaenoic acid (DHA) and decreased numbers of nigrostriatal dopamine neurons. The objective of this application is to identify mechanisms by which an n-3 PUFA-deficient diet leads to decreased numbers of nigrostriatal dopamine neurons, and if this decrease in dopaminergic cell number leads to increased sensitivity to dopaminergic neurotoxins. The hypothesis is that decreased brain DHA content leads to decreased survival of dopamine neurons under normal and pathological conditions. The Specific Aims are to identify candidate mechanisms by which low dietary n-3 PUFA content results in decreased numbers of nigrostriatal dopamine neurons and determine the effects of low dietary n-3 PUFA content on neurotoxic lesion of nigrostriatal dopamine neurons. Expected outcomes from these studies include novel means for preventing and/or slowing progression of Parkinson's disease, as well as increased understanding of the role of phospholipid long chain PUFA composition in neuronal function. Findings may also clarify the underlying pathology of Parkinson's disease, and form a basis for future clinical studies. PUBLIC HEALTH RELEVANCE: Parkinson's disease is a debilitating progressive neurodegenerative disorder affecting 0.1-0.2% of the general population and 2% of people over 65 years of age. The objective of this application is to identify potential factors contributing to the development of Parkinson's disease using a rat model.

描述（由申请人提供）：多巴胺神经元较少的个体似乎增加了导致帕金森氏病的侮辱和神经病理学过程的脆弱性。我们已经表明，在N-3（Omega-3）多不饱和脂肪酸（PUFAS）中，从饮食中饲养的年轻大鼠降低了N-3 PUFA docosahexaenoic（DHA）的大脑水平，并降低了缩质多巴胺神经元的数量。该应用的目的是识别N-3 PUFA缺陷饮食导致鼻叶多巴胺神经元数量减少的机制，并且如果这种饮食饮食的降低会导致多巴胺能细胞的数量减少会导致对多巴胺能神经毒素的敏感性提高。假设是，脑DHA含量降低会导致在正常和病理条件下多巴胺神经元的存活降低。具体的目的是确定候选机制，低饮食中的N-3 PUFA含量会导致数量减少的黑质纹状体多巴胺神经元，并确定低饮食中N-3 PUFA含量对Nigrostriatal多巴胺神经元神经毒性病变的影响。这些研究的预期结果包括预防和/或放缓帕金森氏病进展的新方法，以及对磷脂长链PUFA组成在神经元功能中的作用的了解增加。发现还可以阐明帕金森氏病的潜在病理，并为将来的临床研究构成基础。 公共卫生相关性：帕金森氏病是一种令人衰弱的进步神经退行性疾病，影响了普通人群的0.1-0.2％，而65岁以上的人中有2％。该应用的目的是确定使用大鼠模型导致帕金森氏病发展的潜在因素。