n-3 PUFA supplementation benefits microglial responses to myelin pathology.
n-3 PUFA supplementation benefits microglial responses to myelin pathology.
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N-3 PUFA补充有益于对髓磷脂病理的小胶质反应。
DOI：
10.1038/srep07458
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发表时间：
2014-12-12
影响因子：
4.6
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Chen S;Zhang H;Pu H;Wang G;Li W;Leak RK;Chen J;Liou AK;Hu X
由于小胶质细胞的双重保护和毒性作用，它们代表了改善白色物质完整性的合理但具有挑战性的目标。本研究探讨了欧米茄-3多不饱和脂肪酸（n-3 PUFA）对原代培养物和多发性硬化症（MS）（一种毁灭性脱髓鞘疾病）的cuprizone小鼠模型中髓鞘病理学小胶质细胞反应的影响。二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）是脑内n-3 PUFA的两种主要形式，可抑制IFN-γ和髓磷脂刺激后原代小胶质细胞释放一氧化氮和肿瘤坏死因子-α。DHA和EPA还增强体外髓鞘吞噬作用。因此，n-3 PUFA可以抑制炎症，同时增强有益的免疫反应，如小胶质细胞吞噬作用。体内研究表明，n-3 PUFA补充剂减少了铜腙诱导的脱髓鞘，改善了运动和认知功能。n-3 PUFA的积极作用伴随着小胶质细胞极化向体外和体内有益的M2表型的转变。这些结果表明，n-3 PUFA可能是临床上有用的免疫调节剂，通过一种新的机制，涉及小胶质细胞表型转换的脱髓鞘疾病。
Microglia represent rational but challenging targets for improving white matter integrity because of their dualistic protective and toxic roles. The present study examines the effect of Omega-3 polyunsaturated fatty acids (n-3 PUFAs) on microglial responses to myelin pathology in primary cultures and in the cuprizone mouse model of multiple sclerosis (MS), a devastating demyelination disease. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two main forms of n-3 PUFAs in the brain, inhibited the release of nitric oxide and tumor necrosis factor-α from primary microglia upon IFN-γ and myelin stimulation. DHA and EPA also enhanced myelin phagocytosis in vitro. Therefore, n-3 PUFAs can inhibit inflammation while at the same time enhancing beneficial immune responses such as microglial phagocytosis. In vivo studies demonstrated that n-3 PUFA supplementation reduced cuprizone-induced demyelination and improved motor and cognitive function. The positive effects of n-3 PUFAs were accompanied by a shift in microglial polarization toward the beneficial M2 phenotype both in vitro and in vivo. These results suggest that n-3 PUFAs may be clinically useful as immunomodulatory agents for demyelinating diseases through a novel mechanism involving microglial phenotype switching.
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影响因子：
15.1
作者：
Kong, Weimin;Yen, Jui-Hung;Ganea, Doina
通讯作者：
Ganea, Doina
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
影响因子：
25
作者：
Miron, Veronique E.;Boyd, Amanda;Zhao, Jing-Wei;Yuen, Tracy J.;Ruckh, Julia M.;Shadrach, Jennifer L.;van Wijngaarden, Peter;Wagers, Amy J.;Williams, Anna;Franklin, Robin J. M.;Ffrench-Constant, Charles
通讯作者：
Ffrench-Constant, Charles
影响因子：
4.2
作者：
Ajmone-Cat, Maria Antonietta;Salvatori, Maria Lavinia;Minghetti, Luisa
通讯作者：
Minghetti, Luisa
影响因子：
16.2
作者：
Calon, F;Lim, GP;Cole, GM
通讯作者：
Cole, GM