Giacobbe Juliette, Benoiton Bonnie, Zunszain Patricia, Pariante Carmine M, Borsini Alessandra
Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
Guy's King's and St. Thomas' School of Life Science and Medicine, King's College London, London, United Kingdom.
Front Psychiatry. 2020 Feb 28;11:122. doi: 10.3389/fpsyt.2020.00122. eCollection 2020.
Inflammation has been identified as one of the main pathophysiological mechanisms underlying neuropsychiatric and neurodegenerative disorders. Despite the role of inflammation in those conditions, there is still a lack of effective anti-inflammatory therapeutic strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) can reduce depressive symptoms and exert anti-inflammatory action putatively by the production of distinct n-3 PUFA-derived metabolites, such as resolvins D (RvD) and E (RvE) series, maresins (MaR) and protectins (PD), which are collectively named specialized pro-resolving mediators (SPMs) and act as strong anti-inflammatory agents. In this review we summarize evidence showing the effects of treatment with those metabolites in pre-clinical models of psychiatric, neurodegenerative and neurological disorders. A total of 25 pre-clinical studies were identified using the PubMed database. Overall, RvD and RvE treatment improved depressive-like behaviors, whereas protectins and maresins ameliorated neurological function. On a cellular level, RvDs increased serotonin levels in a model of depression, and decreased gliosis in neurodegenerative disorders. Protectins prevented neurite and dendrite retraction and apoptosis in models of neurodegeneration, while maresins reduced cell death across all studies. In terms of mechanisms, all SPMs down-regulated pro-inflammatory cytokines. Resolvins activated mTOR and MAP/ERK signaling in models of depression, while resolvins and maresins activated the NF-κB pathway in models of neurodegeneration and neurological disorders. Our review indicates a potential promising approach for tailored therapy with n-3 PUFAs-derived metabolites in the treatment of psychiatric, neurodegenerative, and neurological conditions.
炎症已被确定为神经精神疾病和神经退行性疾病的主要病理生理机制之一。尽管炎症在这些疾病中发挥作用，但仍缺乏有效的抗炎治疗策略。ω-3多不饱和脂肪酸（n-3 PUFAs）可以减轻抑郁症状，并可能通过产生独特的n-3多不饱和脂肪酸衍生代谢物发挥抗炎作用，这些代谢物包括消退素D（RvD）和E（RvE）系列、maresins（MaR）和保护素（PD），它们统称为特殊促消退介质（SPMs），并作为强效抗炎剂发挥作用。在本综述中，我们总结了证据，表明这些代谢物在精神、神经退行性和神经疾病的临床前模型中的治疗效果。使用PubMed数据库共鉴定出25项临床前研究。总体而言，RvD和RvE治疗改善了抑郁样行为，而保护素和maresins改善了神经功能。在细胞水平上，RvD在抑郁症模型中增加了血清素水平，并在神经退行性疾病中减少了胶质细胞增生。保护素在神经退行性疾病模型中预防了神经突和树突回缩以及细胞凋亡，而maresins在所有研究中均减少了细胞死亡。在机制方面，所有SPMs均下调促炎细胞因子。消退素在抑郁症模型中激活了mTOR和MAP/ERK信号通路，而消退素和maresins在神经退行性疾病和神经疾病模型中激活了NF-κB通路。我们的综述表明，用n-3多不饱和脂肪酸衍生代谢物进行定制治疗在治疗精神、神经退行性和神经疾病方面具有潜在的前景。
