Mechanism of omega-6 and omega-3 fatty acid transport across the blood brain barrier

omega-6 和 omega-3 脂肪酸跨血脑屏障转运的机制

• 批准号: 418033-2012
• 负责人: Hatch, Grant
• 金额: $ 1.82万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506379
• 关键词: Mechanism; omega; fatty; acid; transport

Fatty acids (FAs) are important to both the developing and mature central nervous system. While the brain can make some fatty acids, there are a number of polyunsaturated fatty acids (PUFAs) including linoleic acid (LA) and alpha linolenic acid (ALA) that must be obtained through the diet. In addition, the brain has a limited ability to make key essential omega-6 and omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These essential fatty acids are absorbed into the bloodstream and enter the brain through brain microvessel endothelial cells that form the blood-brain barrier (BBB). In addition, how proinflammatory FAs such as arachidonic acid (AA) enter into the brain and alter brain function is unknown. The proposed research will examine how FA transport across the BBB occurs with a focus on the PUFAs which are primarily obtained through the diet and on AA, a known proinflammatory FA. Our hypothesis is that the essential PUFAs, ALA, EPA and DHA undergo transport across the BBB through specific fatty acid transport proteins expressed in the brain microvessel endothelial cells and that AA may dramatically alter not only BBB FA transport but also other membrane transport properties. The objectives of the proposal are to: 1. Determine the mechanisms for transport of omega-6 and omega-3 fatty acids across the BBB., 2. Examine the cellular processing of these FAs in the brain microvasculature., 3. Evaluate the effects of both short-term (i.e. 2-60 min) and long-term (i.e. 24-48 h) exposure of FAs on BBB function. The proposed studies will provide important information concerning the mechanisms involved in PUFA transport and distribution in the brain and the effects of PUFAs on BBB function. Given the evidence concerning the vital importance of PUFA in human brain function, the proposed studies are fundamental to the application of various PUFA in the development of the brain and the treatment of central nervous system related diseases such as Alzheimer's disease , depression, schizophrenia, attention deficit and hyperactivity disorders.

脂肪酸(FA)对发育和成熟的中枢神经系统都很重要。虽然大脑可以制造一些脂肪酸，但也有许多多不饱和脂肪酸(PUFAs)，包括亚油酸(LA)和阿尔法亚麻酸(ALA)，必须通过饮食获得。此外，大脑制造关键必需的omega-6和omega-3多不饱和脂肪酸的能力有限，如二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)。这些必需的脂肪酸被血液吸收，并通过形成血脑屏障(BBB)的脑微血管内皮细胞进入大脑。此外，花生四烯酸(AA)等促炎FAs是如何进入大脑并改变大脑功能的，目前尚不清楚。这项拟议的研究将研究FA如何通过血脑屏障转运，重点关注主要通过饮食获得的多不饱和脂肪酸和AA，一种已知的促炎性FA。我们的假设是，必需的多不饱和脂肪酸、丙氨酸、EPA和DHA通过脑微血管内皮细胞表达的特定脂肪酸转运蛋白通过血脑屏障进行转运，AA不仅可能显著改变血脑屏障FA的转运，还可能显著改变其他膜的转运特性。该提案的目的是：1.确定omega-6和omega-3脂肪酸通过血脑屏障的运输机制；2.研究这些脂肪酸在脑微血管中的细胞加工；3.评估短期(即2-60分钟)和长期(即24-48小时)暴露对血脑屏障功能的影响。这些研究将为多不饱和脂肪酸在脑内的转运和分布机制以及多不饱和脂肪酸对血脑屏障功能的影响提供重要信息。鉴于有证据表明多不饱和脂肪酸对人类大脑功能至关重要，拟议的研究对于各种多不饱和脂肪酸在大脑发育和治疗中枢神经系统相关疾病(如阿尔茨海默病、抑郁症、精神分裂症、注意力缺陷和多动障碍)方面的应用至关重要。