Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants.
Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants.
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DOI：
10.1016/j.bbi.2017.05.006
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Zunszain PA
中科院分区：
文献类型：
--
作者：
Borsini A;Alboni S;Horowitz MA;Tojo LM;Cannazza G;Su KP;Pariante CM;Zunszain PA
炎症和神经发生减少与抑郁症的病理生理学有关。IL-1β抑制人海马前体细胞的神经发生EPA、DHA、舍曲林和文拉法辛可防止IL-1β诱导的神经发生减少。EPA和DHA逆转了IL-1β诱导的犬尿氨酸水平增加。EPA、DHA、舍曲林和文拉法辛可降低IDO和KMO mRNA的上调。炎症增加和神经发生减少都与重性抑郁症的病理生理学有关。我们之前已经描述了白细胞介素-1（IL-1）β，一种在抑郁症患者中增加的促炎细胞因子，如何减少人类海马祖细胞的神经发生。在这里，使用相同的人类体外模型，我们展示了omega-3（ω-3）多不饱和脂肪酸和常规抗抑郁药如何逆转神经发生的这种减少，同时差异性地影响犬尿氨酸途径。我们允许神经细胞在IL-1β（10 ng/ml）和选择性5-羟色胺再摄取抑制剂舍曲林（1 µM）、5-羟色胺和去甲肾上腺素再摄取抑制剂文拉法辛（1 µM）或ω-3脂肪酸二十碳五烯酸（EPA，10 µM）或二十二碳六烯酸（DHA，10 µM）存在下增殖3天并进一步分化7天。与这些化合物中的每一种共孵育逆转了IL-1β诱导的神经发生（DCX-和MAP 2-阳性神经元）的减少，表明了保护作用。此外，EPA和DHA还逆转了IL-1β诱导的犬尿氨酸增加以及吲哚胺-2，3-双加氧酶（IDO）的mRNA水平;而DHA和舍曲林逆转了IL-1β诱导的喹啉酸增加和犬尿氨酸3-单加氧酶（KMO）的mRNA水平。我们的研究结果表明，单胺能抗抑郁药和ω-3脂肪酸对IL-1β引起的神经发生减少具有共同作用，但通过共同和不同的犬尿氨酸途径相关机制起作用。进一步表征其个体特性将有利于改善未来的个性化医疗方法。
Inflammation and reduced neurogenesis are associated with the pathophysiology of depression. IL-1β decreased neurogenesis in human hippocampal progenitor cells. EPA, DHA, sertraline and venlafaxine prevented the IL-1β-induced reduction in neurogenesis. EPA and DHA reversed the IL-1β-induced increase in kynurenine levels. EPA, DHA, sertraline and venlafaxine decreased the upregulation of IDO and KMO mRNA. Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3 days and further differentiate for 7 days in the presence of IL-1β (10 ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1 µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1 µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10 µM) or docosahexaenoic acid (DHA, 10 µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach.
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DOI：
10.1038/npp.2012.248
发表时间：
2013-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11
作者：
Anacker, C.;Zunszain, P. A.;Cattaneo, A.;Carvalho, L. A.;Garabedian, M. J.;Thuret, S.;Price, J.;Pariante, C. M.
通讯作者：
Pariante, C. M.
影响因子：
3.6
作者：
Elgarf, Al-Shaimaa A.;Aboul-Fotouh, Sawsan;Abdel-Tawab, Ahmed M.
通讯作者：
Abdel-Tawab, Ahmed M.
影响因子：
11
作者：
Goshen, I.;Kreisel, T.;Yirmiya, R.
通讯作者：
Yirmiya, R.
影响因子：
7.6
作者：
Hannestad, Jonas;DellaGioia, Nicole;Bloch, Michael
通讯作者：
Bloch, Michael