Institute of Clinical Pharmacy and Pharmacology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
Department of Cardiology, Jining First People's Hospital, Jining Medical University, Jining, 272000, China.
Eur J Nutr. 2018 Apr;57(3):893-906. doi: 10.1007/s00394-016-1373-z. Epub 2017 Jan 5.
Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions.
Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 μg/kg every other day).
Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1β, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO supplementation attenuated the LPS-induced abnormal behavior and brain inflammatory response. Concurrent with the antidepressant action, FO also reduced LPS-induced oxidative reactions and neural apoptosis in the rat brain, as evidenced by decreased malondialdehyde (MDA) production, increased catalase activities and inhibited pro-apoptotic protein Bax mRNA expression. In addition, FO inhibited activation of NF-κB and iNOS induced by LPS. Interestingly, we found FO suppressed the activation of the inflammasome NLRP3 and ionotropic purinergic receptor P2X7R evoked by LPS, suggesting a potential anti-inflammatory mechanism for PUFAs. Besides, FO also restored the LPS-induced neurochemical disturbance, especially the balance between serotonin and kynurenine branches of tryptophan metabolism, which is tightly associated with depression.
These findings provide novel insights into the antidepressant action of PUFAs and further strengthen the link between inflammation and depression.
抑郁症常与炎症有关，而主要存在于鱼油中的ω-3 多不饱和脂肪酸（PUFA）具有抗炎特性。尽管有研究表明 PUFAs 具有抗抑郁作用，但直接将 PUFAs 的神经免疫调节特性与抗抑郁作用联系起来的证据有限。
因此，我们评估了鱼油（FO）补充剂对重复外周免疫挑战（LPS）后大鼠行为变化、前额皮质和海马中炎症细胞因子表达和氧化反应的影响，LPS 给药为 2 周（每隔一天 500μg/kg）。
重复 LPS 给药使大鼠产生抑郁样状态，并增加了前额皮质和海马中促炎细胞因子（包括 1L-1β、1L-6 和 TNF-α）的 mRNA 表达。FO 补充剂减轻了 LPS 诱导的异常行为和大脑炎症反应。与抗抑郁作用一致，FO 还降低了 LPS 诱导的大鼠大脑中的氧化反应和神经细胞凋亡，表现为丙二醛（MDA）生成减少、过氧化氢酶活性增加和促凋亡蛋白 Bax mRNA 表达抑制。此外，FO 抑制了 LPS 诱导的 NF-κB 和 iNOS 的激活。有趣的是，我们发现 FO 抑制了 LPS 诱导的 NLRP3 炎症小体和离子型嘌呤能受体 P2X7R 的激活，这表明 PUFAs 具有潜在的抗炎机制。此外，FO 还恢复了 LPS 诱导的神经化学紊乱，特别是色氨酸代谢的 5-羟色胺和犬尿氨酸分支之间的平衡，这与抑郁症密切相关。
这些发现为 PUFAs 的抗抑郁作用提供了新的见解，并进一步加强了炎症与抑郁症之间的联系。
