Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
复制标题
DOI：
10.1007/s12035-015-9228-9
复制
发表时间：
2016-07-01
影响因子：
5.1
通讯作者：
Bernoud-Hubac, Nathalie
中科院分区：
文献类型：
--
作者：
Hachem, Mayssa;Geloen, Alain;Bernoud-Hubac, Nathalie
二十二碳六烯酸 (DHA) 是脑组织中正常大脑发育和功能所需的主要必需 omega-3 脂肪酸。观察到阿尔茨海默氏症和帕金森氏症等神经退行性疾病中大脑 DHA 的变化。大脑有针对性地摄入 DHA 可以弥补这些缺陷。当血液中的 DHA 在溶血磷脂酰胆碱的 sn-2 位被酯化时，可以更有效地穿过血脑屏障。我们使用结构化磷脂酰胆碱来模拟 2-二十二碳六烯酰-lysoPC (lysoPC-DHA)，命名为 AceDoPC (1-乙酰基,2-二十二碳六烯酰-甘油磷酸胆碱)，它可以被认为是生理学 lysoPC-DHA 的稳定形式，并且在实验性缺血性中风中具有神经保护作用。本研究的目的是调查与其他形式的脂肪酸相比，AceDoPC 是否是 DHA 向大脑的相关传递形式。通过结合体外和体内实验，我们的研究结果首次报告，与含 DHA 的 PC 和非酯化 DHA 相比，AceDoPC 是 DHA 到大脑的特殊且特异性的载体。我们还表明 AceDoPC 部分水解为 lysoPC-DHA。大鼠大脑的离体放射自显影显示，AceDoPC 中的 DHA 位于特定的大脑区域，在记忆、思维和认知功能中发挥着关键作用。最后，使用分子建模方法，我们证明静电势和亲脂势在 AceDoPC 和 lysoPC-DHA 表面的分布非常相似。我们的研究结果表明，AceDoPC 是一种将 DHA 特异性靶向大脑的有效方法，这将为神经系统疾病提供潜在的预防和治疗方法。
Docosahexaenoic acid (DHA) is the main essential omega-3 fatty acid in brain tissues required for normal brain development and function. An alteration of brain DHA in neurodegenerative diseases such as Alzheimer's and Parkinson's is observed. Targeted intake of DHA to the brain could compensate for these deficiencies. Blood DHA is transported across the blood-brain barrier more efficiently when esterified at the sn-2 position of lyso-phosphatidylcholine. We used a structured phosphatidylcholine to mimic 2-docosahexaenoyl-lysoPC (lysoPC-DHA), named AceDoPC (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that may be considered as a stabilized form of the physiological lysoPC-DHA and that is neuroprotective in experimental ischemic stroke. The aim of the present study was to investigate whether AceDoPC is a relevant delivery form of DHA to the brain in comparison with other forms of the fatty acid. By combining in vitro and in vivo experiments, our findings report for the first time that AceDoPC is a privileged and specific carrier of DHA to the brain, when compared with DHA-containing PC and non-esterified DHA. We also show that AceDoPC was hydrolyzed, in part, into lysoPC-DHA. Ex vivo autoradiography of rat brain reveals that DHA from AceDoPC was localized in specific brain regions playing key roles in memory, thoughts, and cognitive functions. Finally, using molecular modeling approaches, we demonstrate that electrostatic and lipophilic potentials are distributed very similarly at the surfaces of AceDoPC and lysoPC-DHA. Our findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases.