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

描述（由申请人提供）：黑质纹状体多巴胺神经元较少的个体似乎更容易受到损伤和导致帕金森病的神经病理过程。我们已经证明，从受孕开始，在低n-3 （omega-3）多不饱和脂肪酸（PUFAs）饮食中长大的年轻成年大鼠，大脑中n-3 PUFA二十二碳六烯酸（DHA）的水平降低，黑质纹状体多巴胺神经元的数量减少。本应用程序的目的是确定n-3 pufa缺乏饮食导致黑质纹状体多巴胺神经元数量减少的机制，以及多巴胺能细胞数量的减少是否导致对多巴胺能神经毒素的敏感性增加。假设在正常和病理条件下，脑DHA含量降低导致多巴胺神经元存活减少。具体目的是确定低饲粮n-3 PUFA含量导致黑质纹状体多巴胺神经元数量减少的候选机制，并确定低饲粮n-3 PUFA含量对黑质纹状体多巴胺神经元神经毒性损伤的影响。这些研究的预期结果包括预防和/或减缓帕金森病进展的新方法，以及增加对磷脂长链PUFA组成在神经元功能中的作用的理解。研究结果也可能阐明帕金森病的潜在病理，并为未来的临床研究奠定基础。

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.