Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.
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右美托咪定降低了脂多糖诱导的神经炎症,疾病行为和Anhedonia。

DOI:
10.1371/journal.pone.0191070
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Hsing CH
Hsing CH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yeh CH;Hsieh LP;Lin MC;Wei TS;Lin HC;Chang CC;Hsing CH

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外周先天性免疫反应可能通过激活小胶质细胞、产生过多的细胞因子和神经炎症而诱导疾病行为。右美托咪定(Dex)具有抗炎作用。本研究观察了地塞米松对脂多糖(LPS)诱导的小鼠神经炎症和病态行为的影响。BALB/c小鼠腹腔内(i. p.)注射Dex(50 ug/kg)或溶媒。1小时后,将小鼠注射(i. p.)大肠杆菌LPS(0.33mg/kg)或生理盐水(每组n = 6)。我们分析了小鼠24小时的食物和水摄入量、体重减轻和蔗糖偏好。我们还测定了小鼠大脑中小胶质细胞的活化和细胞因子的表达。在体外,我们确定细胞因子的表达在LPS处理的BV-2小胶质细胞与或没有地塞米松治疗。在Dex预处理的小鼠中,LPS诱导的疾病行为(厌食、体重减轻和社交退缩)减弱,小胶质细胞活化低于溶剂对照。LPS攻击小鼠脑中TNF-α、MCP-1、吲哚胺2,3双加氧酶(IDO)、caspase-3和iNOS的mRNA表达增加,Dex可降低这些mRNA表达,但溶媒不能降低这些mRNA表达。右美托咪定减少LPS诱导的小鼠脑神经炎症,并调节了恶心行为中与奎宁相关的变化。
Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex) has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS)-induced neuroinflammation and sickness behavior in mice. BALB/c mice were intraperitoneally (i.p.) injected with Dex (50 ug/kg) or vehicle. One hour later, the mice were injected (i.p.) with Escherichia coli LPS (0.33 mg/kg) or saline (n = 6 in each group). We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment. In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal) were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO), caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle. Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.
DOI: 10.1006/bbrc.1996.1112
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