Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.
Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing.
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发表时间：
2004
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通讯作者：
J. Bourre
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作者：
J. Bourre
在各种器官中，在大脑中，最广泛研究的脂肪酸是omega-3脂肪酸。α-亚麻酸（18：3 omega 3）缺乏会改变膜的结构和功能，并诱导轻微的脑功能障碍，如动物模型和随后的人类婴儿所示。尽管大脑在物质上是一个与其他器官一样的器官，也就是说，大脑是由饮食中存在的物质（有时是完全由饮食中存在的物质）精心制作的，但长期以来，人们并不认为食物会影响大脑的结构，从而影响其功能。脂质，特别是ω-3脂肪酸，为饮食（营养素）对大脑结构和功能的影响提供了第一个连贯的实验证明。事实上，大脑是脂肪组织之后最富含脂质的器官，其唯一的作用是参与膜结构。首先，研究表明，培养的脑细胞的分化和功能不仅需要α-亚麻酸（omega-3，omega-3家族的主要成分），而且还需要非常长的omega-3和omega-6碳链（1）。然后证明α-亚麻酸缺乏会改变大脑发育的过程，扰乱脑细胞膜、神经元、少突胶质细胞和星形胶质细胞的组成和理化性质（2）。这导致物理化学变化，诱导生化和生理扰动，并导致神经感觉和行为紊乱（3）。因此，存在于婴儿（早产儿和足月儿）配方奶中的多不饱和脂肪酸（特别是ω-3）的性质会影响视觉和大脑能力，包括智力。此外，膳食ω-3脂肪酸肯定涉及预防心血管疾病的某些方面（包括在脑血管形成水平），以及一些神经精神障碍，特别是抑郁症，以及痴呆症，特别是阿尔茨海默病。最近的研究结果表明，饮食中α-亚麻酸缺乏会导致某些大脑结构比其他结构更明显的异常，因为额叶皮质和脑垂体受到的影响更严重。这些选择性损害伴随着行为障碍，尤其影响某些测试（习惯化、适应新情况）。生化和行为异常可通过膳食磷脂补充剂部分逆转，特别是富含omega-3的蛋黄提取物或猪脑。一项剂量效应研究表明，动物磷脂比植物磷脂更有效地逆转α-亚麻酸缺乏的后果，部分原因是它们提供了非常长的预制链。α-亚麻酸缺乏会通过轻微改变感觉器官的功效和影响某些大脑结构来降低对快乐的感知。与听力、视力和嗅觉有关的听力、视力和嗅觉障碍是由于大脑有关部分的功效下降和感觉受体，特别是内耳或视网膜的障碍。例如，在α-亚麻酸缺乏的受试者中，给定的甜味感知水平需要更大量的糖。鉴于西方人的饮食习惯，由于从未观察到omega-6脂肪酸缺乏，因此尚未研究其对大脑的影响。相比之下，ω-9脂肪酸缺乏症，特别是油酸缺乏症，会导致许多组织中这种脂肪酸的减少，除了大脑（但坐骨神经受到影响）。因此，这种脂肪酸的合成量不足，至少在妊娠-哺乳期是这样，这意味着需要从饮食中摄入。必须记住，神经元的组织在出生前几周就几乎完成了，并且这些神经元在受试者的一生中都存在。因此，在生命的任何阶段，这些神经元的任何干扰，它们的连接的改变，以及它们的成分的周转受损，都会加速衰老。从亚油酸和α-亚麻酸合成长链多不饱和脂肪酸的酶活性在大脑中是非常有限的：因此，这个器官依赖于外源性供应。因此，对大脑至关重要的脂肪酸是花生四烯酸和宫颈酸，来源于饮食，除非它们是由肝脏从亚油酸和α-亚麻酸合成的。与年龄相关的肝脏去饱和酶活性（参与长链的合成，以及延长酶）的降低可损害大脑膜的周转。在许多结构中，特别是在额叶皮质中，在衰老过程中观察到颈酸和花生四烯酸的减少，主要与磷脂酰乙醇胺（主要以缩醛磷脂的形式）的减少有关。在衰老过程中，大脑中多不饱和脂肪酸的过氧化物酶体氧化减少，参与膜脂肪酸的周转减少，这也是有效保护免受自由基过氧化作用的降低。
Among various organs, in the brain, the fatty acids most extensively studied are omega-3 fatty acids. Alpha-linolenic acid (18:3omega3) deficiency alters the structure and function of membranes and induces minor cerebral dysfunctions, as demonstrated in animal models and subsequently in human infants. Even though the brain is materially an organ like any other, that is to say elaborated from substances present in the diet (sometimes exclusively), for long it was not accepted that food can have an influence on brain structure, and thus on its function. Lipids, and especially omega-3 fatty acids, provided the first coherent experimental demonstration of the effect of diet (nutrients) on the structure and function of the brain. In fact the brain, after adipose tissue, is the organ richest in lipids, whose only role is to participate in membrane structure. First it was shown that the differentiation and functioning of cultured brain cells requires not only alpha-linolenic acid (the major component of the omega-3, omega3 family), but also the very long omega-3 and omega-6 carbon chains (1). It was then demonstrated that alpha-linolenic acid deficiency alters the course of brain development, perturbs the composition and physicochemical properties of brain cell membranes, neurones, oligodendrocytes, and astrocytes (2). This leads to physicochemical modifications, induces biochemical and physiological perturbations, and results in neurosensory and behavioural upset (3). Consequently, the nature of polyunsaturated fatty acids (in particular omega-3) present in formula milks for infants (premature and term) conditions the visual and cerebral abilities, including intellectual. Moreover, dietary omega-3 fatty acids are certainly involved in the prevention of some aspects of cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, notably Alzheimer's disease. Recent results have shown that dietary alpha-linolenic acid deficiency induces more marked abnormalities in certain cerebral structures than in others, as the frontal cortex and pituitary gland are more severely affected. These selective lesions are accompanied by behavioural disorders more particularly affecting certain tests (habituation, adaptation to new situations). Biochemical and behavioural abnormalities are partially reversed by a dietary phospholipid supplement, especially omega-3-rich egg yolk extracts or pig brain. A dose-effect study showed that animal phospholipids are more effective than plant phospholipids to reverse the consequences of alpha-linolenic acid deficiency, partly because they provide very long preformed chains. Alpha-linolenic acid deficiency decreases the perception of pleasure, by slightly altering the efficacy of sensory organs and by affecting certain cerebral structures. Age-related impairment of hearing, vision and smell is due to both decreased efficacy of the parts of the brain concerned and disorders of sensory receptors, particularly of the inner ear or retina. For example, a given level of perception of a sweet taste requires a larger quantity of sugar in subjects with alpha-linolenic acid deficiency. In view of occidental eating habits, as omega-6 fatty acid deficiency has never been observed, its impact on the brain has not been studied. In contrast, omega-9 fatty acid deficiency, specifically oleic acid deficiency, induces a reduction of this fatty acid in many tissues, except the brain (but the sciatic nerve is affected). This fatty acid is therefore not synthesized in sufficient quantities, at least during pregnancy-lactation, implying a need for dietary intake. It must be remembered that organization of the neurons is almost complete several weeks before birth, and that these neurons remain for the subject's life time. Consequently, any disturbance of these neurons, an alteration of their connections, and impaired turnover of their constituents at any stage of life, will tend to accelerate ageing. The enzymatic activities of sytivities of synthesis of long-chain polyunsaturated fatty acids from linoleic and alpha-linolenic acids are very limited in the brain: this organ therefore depends on an exogenous supply. Consequently, fatty acids that are essential for the brain are arachidonic acid and cervonic acid, derived from the diet, unless they are synthesized by the liver from linoleic acid and alpha-linolenic acid. The age-related reduction of hepatic desaturase activities (which participate in the synthesis of long chains, together with elongases) can impair turnover of cerebral membranes. In many structures, especially in the frontal cortex, a reduction of cervonic and arachidonic acids is observed during ageing, predominantly associated with a reduction of phosphatidylethanolamines (mainly in the form of plasmalogens). Peroxisomal oxidation of polyunsaturated fatty acids decreases in the brain during ageing, participating in decreased turnover of membrane fatty acids, which are also less effectively protected against peroxidation by free radicals.