Lipid Nutrition and the Brain

青少年行为和多巴胺有效性对膳食n-3脂肪酸含量敏感。了解影响行为健康的环境因素对于有精神疾病风险的个体的成功预防策略至关重要。饮食中N-3多不饱和脂肪酸（PUFAs）的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到成年早期。因此，青春期可能是饮食对环境造成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在假设4-5年前，当当前青少年的父母出生时，饮食趋势就开始减少这些PUFAS的摄入。研究人员比较了喂食n-3 PUFA充足和缺乏饮食的青少年和成年大鼠在一系列任务中的行为表现以及多巴胺相关神经传递的标志物。在青少年中，连续几代的n-3 PUFA缺乏会导致认知和动机行为的模式选择性和任务依赖性损伤，这与在成人中观察到的缺陷不同。虽然这种饮食不足影响了两组青少年中多巴胺相关蛋白的表达，但对成年人没有影响，酪氨酸羟化酶的表达增加对背纹状体有选择性。这些数据支持营养对青少年最佳认知和情感功能的贡献。（1）

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)