Mifepristone attenuates depression-like changes induced by chronic central administration of interleukin-1β in rats
Mifepristone attenuates depression-like changes induced by chronic central administration of interleukin-1β in rats
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米非司酮减轻大鼠长期中枢注射白细胞介素-1β 引起的抑郁样变化
DOI：
10.1016/j.bbr.2018.03.033
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发表时间：
2018-07
影响因子：
2.7
通讯作者：
宋采
中科院分区：
文献类型：
--
作者：
张永平;宋采
促炎症细胞因子，如白细胞介素1β的增加，可能在抑郁症的病因中起重要作用，因为它们导致下丘脑-垂体-肾上腺轴释放糖皮质激素，并导致5-羟色胺和去甲肾上腺素神经传递功能障碍。持续升高的GC可能激活小胶质细胞，诱导神经炎症，抑制星形胶质细胞产生神经营养因子，从而导致神经元凋亡。在这里，我们验证了糖皮质激素受体(GR)拮抗剂米非司酮(RU486)可能通过调节小胶质细胞和星形胶质细胞的神经炎症和神经营养因子功能来减轻IL-1β诱导的抑郁样行为的假说。大鼠侧脑室注射IL-1β(10 ng)和/或皮下注射RU486，连续14天。观察大鼠抑郁行为、血清皮质酮浓度、促炎症细胞因子(肿瘤坏死因子-α、白介素6)水平、杏仁核CD11b、胶质纤维酸性蛋白和神经营养因子及其受体TrkB、p75、GFRα-1和GFRα-2的表达。与对照组相比，IL-1-β组大鼠在旷场实验中的站立成绩显著降低，排便次数明显增加，高架迷宫的开合时间比和蔗糖偏好显著降低，血清皮质酮水平显著升高。IL-1β还可降低胶质纤维酸性蛋白、脑源性神经营养因子、胶质细胞源性神经营养因子及其受体α-CD11b的表达，增加CD11b、前脑源性神经营养因子、p75的表达和促炎细胞因子(α、IL-6)的浓度。结论：RU486可能通过抑制小胶质细胞和炎症反应，促进星形胶质细胞恢复神经营养因子功能，从而改善β诱导的抑郁样改变。结论：RU486治疗可明显减轻IL-1α诱导的抑郁样改变。
Increased proinflammatory cytokines, such as interleukin (IL)-1β, may play an important role in the etiology of depression because they cause the hypothalamic–pituitary–adrenal axis to release glucocorticoids (GC) and induce dysfunction of serotonin and norepinephrine neurotransmission. Sustained increase in GC may activate microglia to induce neuroinflammation, and suppress astrocytes to produce neurotrophins, which lead to neuronal apoptosis. Here, we tested the hypothesis that glucocorticoid receptor (GR) antagonist mifepristone (RU486) may attenuate IL-1β-induced depression-like behavior by regulating the neuroinflammation and neurotrophin functions of microglia and astrocytes. Rats received intracerebroventricular injections of IL-1β (10 ng) and/or subcutaneous injections of RU486 for 14 days. Then animal depression-like behaviors, serum corticosterone concentration, the levels of pro-inflammatory cytokines (TNF-α, IL-6), mRNA and protein expressions of CD11b, GFAP and neurotrophins (pro-BDNF, BDNF, GDNF and their receptors TrkB, p75, GFRα-1 and GFRα-2) in the amygdala were studied. Compared to controls, significantly decreased rearing score and increased defecation in the open field test, decreases in ratio of open/closed time in the elevated plus maze and in sucrose preference, while increased level of corticosterone in the serum were found in the rats administrated with IL-1β. IL-1β administration also reduced the expressions of GFAP, BDNF, GDNF and its receptor GFR-α1, but increased the expressions of CD11b, pro-BDNF, p75 and pro-inflammatory cytokines (TNF-α, IL-6) concentrations. RU486 treatment markedly attenuated these changes induced by IL-1β, except for the expressions of GFR-α1. In conclusion, RU486 may improve depression-like changes by suppressing microglia and inflammation and promoting astrocytes to restore neurotrophin function.
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影响因子：
3.1
作者：
Qian Wang;E. Verweij;H. Krugers;M. Joëls;M. Joëls;D. Swaab;P. Lucassen
通讯作者：
Qian Wang;E. Verweij;H. Krugers;M. Joëls;M. Joëls;D. Swaab;P. Lucassen
影响因子：
5.3
作者：
Ubhi, Kiren;Inglis, Chandra;Mante, Michael;Patrick, Christina;Adame, Anthony;Spencer, Brian;Rockenstein, Edward;May, Verena;Winkler, Juergen;Masliah, Eliezer
通讯作者：
Masliah, Eliezer
影响因子：
2.9
作者：
Block T;Petrides G;Kushner H;Kalin N;Belanoff J;Schatzberg A
通讯作者：
Schatzberg A
影响因子：
4.3
作者：
C. Song;Horrobin Df;Leonard Be
通讯作者：
C. Song;Horrobin Df;Leonard Be
糖皮质激素介导了神经炎性启动，NLRP3炎性体和危险信号HMGB1的短期高脂饮食诱导。
影响因子：
3.4
作者：
Sobesky JL;D'Angelo HM;Weber MD;Anderson ND;Frank MG;Watkins LR;Maier SF;Barrientos RM
通讯作者：
Barrientos RM