Lipid Nutrition and the Brain

青少年行为和多巴胺的利用率对膳食N-3脂肪酸含量敏感。了解有助于行为健康的环境因素对于有精神疾病风险的个人成功预防策略至关重要。N-3多不饱和脂肪酸（PUFA）的饮食缺乏与精神分裂症和情绪障碍有关，这些疾病通常发生在青春期至成年早期。因此，青春期可能是饮食作为环境侮辱的负面影响的关键年龄段。一个涉及连续几代n-3 PUFA缺乏症的大鼠模型是基于这样的假设开发的，即当当前青少年的父母出生时，这些PUFAS的消费量减少的饮食趋势始于4- 50年前。在一系列任务的行为表现，以及多巴胺相关的神经传递的标志物进行了比较，在青少年和成年大鼠喂养n-3多不饱和脂肪酸充足和不足的饮食。在青少年中，连续几代的n-3多不饱和脂肪酸缺乏症在认知和动机行为方面产生了与成年人中观察到的缺陷不同的模式选择性和任务依赖性损害。虽然这种饮食缺乏影响多巴胺相关蛋白的表达在这两个年龄组的青少年，但不是成年人，有一个选择性的背侧纹状体的酪氨酸羟化酶的表达增加。这些数据支持营养对青少年最佳认知和情感功能的贡献。（一） 进食高N-3 PUFA饲料的清醒大鼠脑、心和肝中二十碳五烯酸的动力学二十碳五烯酸（EPA，20：5 n-3）是二十二碳六烯酸（DHA）的前体，可能有益于心血管和大脑健康。定量EPA的体内动力学可能阐明这些影响。1-14在喂食标准EPA-DHA饲料的未麻醉雄性大鼠中静脉输注CEPA 5分钟。分析血浆和微波组织。使用我们的房室模型计算动力学参数。5 min时，脑和心脏中标记EPA的氧化率为31-48%，肝中标记EPA的氧化率为7%。大脑和肝脏前体EPA-CoA池的EPA掺入脂质（主要是磷脂）的速率分别为36和2529 nmol/s/g10（-4），对心脏无显著影响。脱酰-再酰化半衰期为22小时和38- 128分钟。转化为DHA的速率分别为0.65和25.1nmol/s/g10（-4）。EPA的低脑浓度和掺入率以及高氧化表明，如果EPA在脑中具有有益作用，则可能是由于其抑制外周炎症和肝脏转化为生物活性DHA。（二） 大鼠慢性NMDA的神经病理学反应因饮食N-3 PUFA剥夺而恶化，但鱼油补充并未改善。饮食中的长链n-3多不饱和脂肪酸（PUFA）的补充可能是有益的慢性脑部疾病，但这个问题是不同意的on. We检查的影响，饮食n-3 PUFA剥夺或补充，与n-3 PUFA充足的饮食（含有α-亚麻酸18：3 n-3，但没有二十二碳六烯酸DHA，22：6 n-3），对大脑的脂质代谢和兴奋性毒性的标志物，在大鼠长期治疗与NMDA或盐水。断奶后的雄性大鼠维持三种饮食之一15周。12周后，每个饮食组每天腹膜内注射盐水（1 ml/kg）或亚惊厥剂量的NMDA（25 mg/kg），持续另外3周。然后，测量脑脂肪酸浓度和兴奋性毒性和脂肪酸代谢的各种标志物。与饮食充足组相比，n-3缺乏组的脑DHA浓度降低，而n-6二十二碳五烯酸（DPA，22：5 n-6）浓度升高;花生四烯酸（AA，20：4 n-6）浓度不变。这些浓度不受鱼油补充的影响。慢性NMDA增加脑cPLA 2的活性，在每三个组，但n-3 PUFA剥夺或鱼油没有改变cPLA 2的活性或蛋白质与足够的组相比。sPLA 2的表达在三种条件下没有变化，而iPLA 2的表达通过剥夺而减少，但通过补充而没有改变。在N-3 PUFA缺乏大鼠中，NMDA降低了BDNF蛋白，但IL-1、NGF和GFAP的蛋白水平在组间没有差异。N-3 PUFA剥夺显着恶化的几个病理NMDA诱导的变化产生的饮食充足的大鼠，而n-3 PUFA补充不影响NMDA诱导的变化。一旦饮食中有足够的n-3 PUFA含量，补充可能对这种测量的神经病理学并不重要。（三）

ADOLESCENT BEHAVIOR AND DOPAMINE AVAILABILITY ARE SENSITIVE TO DIETARY N-3 FATTY ACID CONTENT. Understanding environmental factors that contribute to behavioral health is critical for successful prevention strategies in individuals at risk for psychiatric disorders. Dietary deficiency of N-3 polyunsaturated fatty acids (PUFAs) has been implicated in schizophrenia and mood disorders, which typically occur during adolescence to early adulthood. Thus, adolescence might be the critical age range for the negative impact of diet as an environmental insult. A rat model involving consecutive generations of n-3 PUFA deficiency was developed on the assumption that dietary trends toward decreased consumption of these PUFAS began 4-5 decades ago when parents of current adolescents were born. Behavioral performance in a range of tasks as well as markers of dopamine-related neurotransmission were compared in adolescents and adult rats fed n-3 PUFA adequate and deficient diets. In adolescents, n-3 PUFA deficiency across consecutive generations produced a modality-selective and task-dependent impairment in cognitive and motivated behavior distinct from the deficits observed in adults. Although this dietary deficiency affected expression of dopamine-related proteins in both age groups in adolescents but not adults, there was an increase in tyrosine hydroxylase expression that was selective to the dorsal striatum. These data support a nutritional contribution to optimal cognitive and affective functioning in adolescents. (1) KINETICS OF EICOSAPENTAENOIC ACID IN BRAIN, HEART AND LIVER OF CONSCIOUS RATS FED A HIGH N-3 PUFA CONTAINING DIET. Eicosapentaenoic acid (EPA, 20:5n-3), a precursor of docosahexaenoic acid (DHA), may benefit cardiovascular and brain health. Quantifying EPA's in vivo kinetics might elucidate these effects. 1-14CEPA was infused i.v. for 5min in unanesthetized male rats fed a standard EPA-DHA diet. Plasma and microwaved tissue were analyzed. Kinetic parameters were calculated using our compartmental model. At 5min, 31-48% of labeled EPA in brain and heart was oxidized, 7% in liver. EPA incorporation rates from brain and liver precursor EPA-CoA pools into lipids, mainly phospholipids, were 36 and 2529nmol/s/g10(-4), insignificant for heart. Deacylation-reacylation half-lives were 22h and 38-128min. Conversion rates to DHA equaled 0.65 and 25.1nmol/s/g10(-4), respectively. The low brain concentration and incorporation rate and high oxidation of EPA suggest that, if EPA has a beneficial effect in brain, it might result from its suppression of peripheral inflammation and hepatic conversion to bioactive DHA. (2) NEUROPATHOLOGICAL RESPONSES TO CHRONIC NMDA IN RATS ARE WORSENED BY DIETARY N-3 PUFA DEPRIVATION BUT ARE NOT AMELIORATED BY FISH OIL SUPPLEMENTATION. Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid 18:3 n-3 but not docosahexaenoic acid DHA, 22:6n-3), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline. Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose of NMDA (25 mg/kg) for 3 additional weeks. Then, brain fatty acid concentrations and various markers of excitotoxicity and fatty acid metabolism were measured. Compared to the diet-adequate group, brain DHA concentration was reduced, while n-6 docosapentaenoic acid (DPA, 22:5n-6) concentration was increased in the n-3 deficient group; arachidonic acid (AA, 20:4n-6) concentration was unchanged. These concentrations were unaffected by fish oil supplementation. Chronic NMDA increased brain cPLA2 activity in each of the three groups, but n-3 PUFA deprivation or fish oil did not change cPLA2 activity or protein compared with the adequate group. sPLA2 expression was unchanged in the three conditions, whereas iPLA2 expression was reduced by deprivation but not changed by supplementation. BDNF protein was reduced by NMDA in N-3 PUFA deficient rats, but protein levels of IL-1β, NGF, and GFAP did not differ between groups. N-3 PUFA deprivation significantly worsened several pathological NMDA-induced changes produced in diet adequate rats, whereas n-3 PUFA supplementation did not affect NMDA induced changes. Supplementation may not be critical for this measured neuropathology once the diet has an adequate n-3 PUFA content. (3)