Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus
Chronic antidepressant treatments resulted in altered expression of genes involved in inflammation in the rat hypothalamus
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DOI：
10.1016/j.ejphar.2013.08.046
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发表时间：
2013-12-05
影响因子：
5
通讯作者：
Brunello, Nicoletta
中科院分区：
文献类型：
--
作者：
Alboni, Silvia;Benatti, Cristina;Brunello, Nicoletta
为了深入了解抗抑郁药的可能免疫靶点，我们评估了用5-羟色胺选择性再摄取抑制剂氟西汀（5 mg/kg，i. p.）或三环化合物丙咪嗪（15 mg/kg，i. p.）。我们把注意力集中在下丘脑上，因为它在确定抑郁症患者所经历的许多躯体症状中起着关键作用。这一大脑区域对表达动机行为也至关重要，参与控制下丘脑-垂体-肾上腺轴活动和应激反应，以及协调生理功能，如睡眠和食物摄入，这些功能在高比例的抑郁症患者中被发现改变。值得注意的是，下丘脑是脑细胞因子表达和功能的关键结构，因为它整合了来自神经，免疫，内分泌系统的信号。通过定量的真实的时间OCR实验，我们证明了氟西汀或丙咪嗪的慢性治疗导致大鼠下丘脑中IL-6和IFN-γ mRNA的减少和IL-4 mRNA的表达增加。此外，我们证明，下丘脑表达的IL-18系统的成员受到慢性抗抑郁治疗的差异。长期给予氟西汀降低IL-8和CX 3CL 1下丘脑的表达，而丙咪嗪的长期治疗降低p11 mRNA。我们的数据表明，下丘脑炎症平衡向抗炎状态的转变可能是氟西汀和丙咪嗪长期治疗的共同作用机制。(C)2013爱思唯尔有限公司版权所有。
To gain insight into the possible immune targets of antidepressant, we evaluated the expression of several inflammatory mediators in the hypothalamus of rats chronically (28 days) treated with the serotonin selective reuptake inhibitor fluoxetine (5 mg/kg, i.p.) or the tricyclic compound imipramine (15 mg/kg, i.p.). We focused our attention on the hypothalamus as it plays a key role in determining many of the somatic symptoms experienced by depressed patients. This brain region, critical also for expression of motivated behaviours, participates in the control of the hypothalamic-pituitary-adrenal axis activity and in stress response as well as coordinates physiological functions such as sleep and food intake that have been found altered in a high percentage of depressed patients. Notably, hypothalamus is a key structure for brain cytokine expression and function as it integrates signals from the neuro, immune, endocrine systems. By means of quantitative Real Time OCR experiments we demonstrated that a chronic treatment with either fluoxetine or imipramine resulted in a reduction of IL-6 and IFN-gamma mRNAs and increased IL-4 mRNA expression in the rat hypothalamus. Moreover, we demonstrated that hypothalamic expression of members of IL-18 system was differentially affected by chronic antidepressant treatments. Chronically administered fluoxetine decreased IL-8 and CX3CL1 hypothalamic expression, while a chronic treatment with imipramine decreased p11 mRNA. Our data suggest that a shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus may represent a common mechanism of action of both the chronic treatments with fluoxetine and imipramine. (C) 2013 Elsevier B.V. All rights reserved.