Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors.
Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors.
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DOI：
10.1016/j.bbi.2016.05.008
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发表时间：
2016-10
影响因子：
15.1
通讯作者：
Sheridan, John F.
中科院分区：
文献类型：
--
作者：
Ramirez, Karol;Sheridan, John F.
为了缓解伴随压力产生的焦虑和抑郁，医生会使用三环类抗抑郁药，比如丙咪嗪。我们之前已经表明，丙咪嗪可逆转压力诱导的社交回避行为，并在压力停止24天后下调小胶质细胞的激活。为了进一步描述丙咪嗪对压力诱导的神经免疫失调以及相关行为变化的影响，本研究的目的是确定丙咪嗪是否：1）改善外周和中枢神经系统中压力诱导的炎症；2）预防与压力相关的焦虑和抑郁样行为。将丙咪嗪（15mg/kg）添加到饮用水中对C57BL/6小鼠进行处理，并使其遭受重复性社交挫败（RSD）。丙咪嗪减弱了血浆中压力诱导的皮质酮和白细胞介素 - 6反应。丙咪嗪降低了骨髓和循环中单核细胞和粒细胞的百分比。然而，在重复性社交挫败后，丙咪嗪没有阻止脾肿大、该器官中与压力相关的粒细胞百分比增加以及脾脏中促炎细胞因子的产生。此外，丙咪嗪消除了遭受重复性社交挫败的小鼠大脑中巨噬细胞的积聚。丙咪嗪阻断了神经炎症信号传导，并预防了与压力相关的焦虑和抑郁样行为。这些数据支持这样一种观点，即单胺能系统的药物调节除了具有抗焦虑和抗抑郁作用外，在压力期间还可能作为一种神经免疫调节剂发挥治疗作用。
In order to relieve anxiety and depression accompanying stress, physicians resort to tricyclic antidepressants, such as imipramine. We had previously shown that imipramine reversed stress-induced social avoidance behavior, and down-regulated microglial activation 24 days after stress cessation. To further characterize the effects of imipramine on stress induced neuroimmune dysregulation and associated changes in behavior, the aims of this study were to determine if imipramine 1) ameliorated stress-induced inflammation in the periphery and central nervous system, and 2) prevented stress related anxiety- and depressive-like behaviors. C57BL/6 mice were treated with imipramine (15mg/kg) in their drinking water, and exposed to repeated social defeat (RSD). Imipramine attenuated stress-induced corticosterone and IL-6 responses in plasma. Imipramine decreased the percentage of monocytes and granulocytes in the bone marrow and circulation. However, imipramine did not prevent splenomegaly, stress-related increased percentage of granulocytes in this organ, and the production of pro-inflammatory cytokines in the spleen, following RSD. Moreover, imipramine abrogated the accumulation of macrophages in the brain in mice exposed to RSD. Imipramine blocked neuroinflammatory signaling and prevented stress-related anxiety- and depressive-like behaviors. These data support the notion that pharmacomodulation of the monoaminergic system, besides exerting anxiolytic and antidepressant effects, may have therapeutic effects as a neuroimmunomodulator during stress.
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影响因子：
5.5
作者：
Avitsur, R;Padgett, DA;Sheridan, JF
通讯作者：
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