Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat
Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat
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米诺环素可改善大鼠由慢性不可预测的轻度应激引起的抑郁行为和神经免疫功能障碍
DOI：
10.1016/j.bbr.2018.07.001
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发表时间：
2019-01
影响因子：
2.7
通讯作者：
宋采
中科院分区：
文献类型：
--
作者：
张才;宋采
活化的小胶质细胞诱导的神经炎症可以刺激下丘脑-垂体-肾上腺（HPA）轴释放糖皮质激素并抑制星形胶质细胞功能，例如减少神经营养因子的产生，这在抑郁症中发生。然而，在抑郁症中，M1（促炎症）和M2（抗炎）小胶质细胞表型之间的平衡以及这两种胶质细胞之间的相互作用尚不清楚。因此，选择慢性不可预测的轻度应激（CIMs）诱导的抑郁模型来研究抑郁和焦虑样行为、皮质酮和相关海马细胞因子的浓度、小胶质细胞和星形胶质细胞标记物的mRNA和蛋白表达。为了证明M1表型激活在抑郁症中的作用，还评估了小胶质细胞抑制剂米诺环素对这些方面的影响。接触CUMS六周后，对行为进行了测试。与对照组相比，BRAS增加血清皮质酮浓度和抑郁样行为，如快感缺乏，无助和焦虑。此外，Cysts增加了小胶质细胞M1标记物CD11b的表达和肿瘤坏死因子（TNF）-α、干扰素（INF）-γ、白细胞介素（IL）-1 β和IL-17的浓度，但降低了M2细胞因子、IL-4、IL-10和IL-13的浓度。同时，Bismuth S抑制星形胶质细胞标志物胶质细胞酸性蛋白（GFAP）、脑源性神经营养因子（BDNF）和TrKB的表达。米诺环素（40 mg/kg，45天）治疗显着减弱CNS诱导的行为异常，这与抑制M1反应，恢复GFAP，BDNF及其受体的表达。总之，CNS诱导的抑郁和焦虑样行为可能是由于M1和M2之间的不平衡以及星形胶质细胞功能受到抑制。米诺环素治疗逆转了M1反应，这与行为正常化有关。
Activated microglia-induced neuroinflammation can stimulate the hypothalamic- pituitary-adrenal (HPA) axis to release glucocorticoids and suppress astrocyte functions, such as reducing neurotrophin production, which occur in depression. However, the balance between M1 (pro-inflammation) and M2 (anti-inflammation) microglial phenotypes and the interaction between these two glial cells are unclear in the depression. Hence, the chronic unpredictable mild stress (CUMS)-induced depression model was chosen to study depression- and anxiety-like behaviors, the concentration of corticosterone and relevant hippocampal cytokines, mRNA and protein expressions of microglial and astrocyte markers. To demonstrate the role of M1 phenotype activation in depression, the effect of microglial inhibitor minocycline on these aspects was also evaluated. Six weeks after CUMS exposure, behaviors were tested. Compared to the control group, CUMS increased serum corticosterone concentration and depression-like behaviors, like anhedonia, helplessness and anxiety. Moreover, CUMS increased microglia M1 marker CD11b expression and tumor necrosis factor (TNF)-α, interferon (INF)-γ, interleukin (IL)-1β and IL-17 concentrations, but decreased the concentration of M2 cytokines, IL-4, IL-10 and IL-13. Meanwhile, CUMS inhibited the expressions of astrocyte marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrKB. Minocycline (40 mg/kg, 45 days) treatment significantly attenuated CUMS-induced behavioral abnormalities, which were associated with the suppressed M1 response, restored GFAP, BDNF and its receptor expression. In conclusion, CUMS-induced depression- and anxiety-like behavior may result from an imbalance between M1 and M2 and suppressed astrocyte function. Minocycline treatment reversed M1 response, which was associated with behavioral normalization.
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影响因子：
3.4
作者：
Papp M;Gruca P;Lason-Tyburkiewicz M;Willner P
通讯作者：
Willner P
影响因子：
4.3
作者：
Xu N;Tang XH;Pan W;Xie ZM;Zhang GF;Ji MH;Yang JJ;Zhou MT;Zhou ZQ
通讯作者：
Zhou ZQ
影响因子：
4.3
作者：
C. Song;Horrobin Df;Leonard Be
通讯作者：
C. Song;Horrobin Df;Leonard Be
影响因子：
3.2
作者：
Jean-Luc Martin;P. Magistretti;I. Allaman
通讯作者：
Jean-Luc Martin;P. Magistretti;I. Allaman
影响因子：
9.3
作者：
Song C;Zhang Y;Dong Y
通讯作者：
Dong Y