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5-HT₁A 受体在鱼油介导的大鼠海马和皮质 BDNF 表达增加中的作用:一种可能的抗抑郁机制。

The role of 5-HT₁A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism.

机构信息

Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, 81.531-990 Curitiba, PR, Brazil.

出版信息

Neuropharmacology. 2012 Jan;62(1):184-91. doi: 10.1016/j.neuropharm.2011.06.017. Epub 2011 Jun 29.

DOI:10.1016/j.neuropharm.2011.06.017
PMID:21740919
Abstract

Epidemiological and dietary studies show that nutritional deficit of omega-3 polyunsaturated fatty acids (ω-3 PUFA) is directly related to the prevalence and severity of depression. Supplementation with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) during critical periods of development (pregnancy and lactation) is essential for cortical maturation, synaptogenesis and myelination, and may also mitigate the risk for cognitive deficits and psychopathologies in young adults. The present study was performed to evaluate the involvement of serotonin (5-HT) receptors, particularly of 5-HT(1A), and hippocampal brain-derived neurotrophic factor (BDNF) expression in the antidepressant effect of ω-3 PUFA supplementation. In Experiment 1, the antidepressant effects of fish oil were assessed by the modified forced swim test in adult rats. The data indicated a robust antidepressant effect produced by this supplementation and that treatment of the rats with WAY 100135 reversed this effect. In Experiment 2, cortical and hippocampal contents of BDNF, 5-HT, dopamine (DA) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), and 3,4-dihydroxyphenylacetic acid (DOPAC), were determined in animals subjected to the same protocol. Increased BDNF expression in the cortex and hippocampus of both age groups was detected. In 90 day-old rats, 5-HT content in the hippocampus was increased, whereas 5-HIAA formation was diminished in the fish oil group. We suggest the occurrence of a reciprocal involvement of 5-HT(1A) receptors activation and the hippocampal BDNF-increased expression mediated by fish oil supplementation. These data corroborate and expand the notion that supplementation with ω-3 PUFA produces antidepressant effects mediated by an increase in serotonergic neurotransmission, particularly in the hippocampus. This article is part of a Special Issue entitled 'Anxiety and Depression'.

摘要

流行病学和饮食研究表明,ω-3 多不饱和脂肪酸(ω-3 PUFA)的营养缺乏与抑郁症的流行和严重程度直接相关。在发育关键期(怀孕和哺乳期)补充二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)对于皮质成熟、突触发生和髓鞘形成至关重要,也可能降低年轻人认知缺陷和精神病理学的风险。本研究旨在评估 5-羟色胺(5-HT)受体,特别是 5-HT(1A),以及海马脑源性神经营养因子(BDNF)表达在 ω-3 PUFA 补充的抗抑郁作用中的参与。在实验 1 中,通过改良强迫游泳试验评估鱼油的抗抑郁作用。数据表明,这种补充具有强大的抗抑郁作用,而用 WAY 100135 处理大鼠则逆转了这种作用。在实验 2 中,在接受相同方案的动物中测定皮质和海马中的 BDNF、5-HT、多巴胺(DA)及其代谢物 5-羟吲哚乙酸(5-HIAA)和 3,4-二羟基苯乙酸(DOPAC)的含量。在两个年龄组的皮质和海马中均检测到 BDNF 表达增加。在 90 天大的大鼠中,海马中的 5-HT 含量增加,而鱼油组的 5-HIAA 形成减少。我们认为 5-HT(1A)受体激活和鱼油补充介导的海马 BDNF 表达增加之间存在相互参与。这些数据证实并扩展了补充 ω-3 PUFA 通过增加 5-羟色胺能神经传递产生抗抑郁作用的观点,特别是在海马中。本文是题为“焦虑和抑郁”的特刊的一部分。

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