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首页> 外文期刊>The European Journal of Neuroscience >Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats.
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Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats.

机译:免疫诱导的大鼠疲劳中脑干扰素和血清素转运蛋白表达的增强。

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Immunologically induced fatigue was induced in rats by intraperitoneal injection of a synthetic double-stranded RNA, polyriboinosinic : polyribocytidylic acid (poly I:C). An injection of poly I:C (3 mg/kg) decreased the daily amounts of spontaneous running wheel activity to approximately 60% of the preinjection level until day 8. Quantitative analysis of mRNA levels demonstrated that interferon-alpha (IFN-alpha) and p38 mitogen-activated protein kinase mRNAs increased in the medial preoptic, paraventricular and ventromedial hypothalamic nuclei and in cortex on both days 1 and 8, while interleukin-1beta and an inhibitor of nuclear factor kappaB (IkappaB)-beta mRNAs increased on day 1, but recovered within a week. Serotonin transporter (5-HTT) mRNA also increased on days 1 and 8 after poly I:C injection in the same brain regions where IFN-alpha mRNA increased. The increased 5-HTT had a functional significance, because in vivo brain microdialysis revealed that an i.p. injection of poly I:C induced a decrease in the extracellular concentration of 5-HT in the prefrontal cortex; the decrease was blocked by local perfusion with a nonselective 5-HT reuptake inhibitor, imipramine. Finally, the poly I:C-induced fatigue was attenuated by a 5-HT1A receptor agonist but not by 5-HT2, 5-HT3 or dopamine D3 agonists. These findings, taken together, suggest that disorders in brain IFN-alpha and 5-HTT expression may be involved in the neuronal mechanisms of the poly I:C-induced fatigue.
机译:通过腹膜内注射合成的双链RNA,多核糖蛋白酸:多核糖酸(poly I:C),在大鼠中诱发免疫学诱发的疲劳。注射聚I:C(3 mg / kg)可使每日自发行走轮活动量降低至注射前水平的约60%,直至第8天。对mRNA水平的定量分析表明,干扰素-α(IFN-alpha)和在第1天和第8天,内侧视前,室旁和下丘脑下丘核以及皮层中的p38丝裂原活化蛋白激酶mRNA增加,而在第1天,白细胞介素1beta和一种核因子kappaB(IkappaB)-beta mRNA的表达增加。但一周之内就恢复了。聚I:C注射后第1天和第8天,在IFN-αmRNA增加的同一大脑区域,血清素转运蛋白(5-HTT)mRNA也增加。增加的5-HTT具有功能意义,因为体内脑微透析显示i.p.注射poly I:C导致前额叶皮层5-HT的细胞外浓度降低;使用非选择性5-HT再摄取抑制剂imipramine局部灌注可阻止这种下降。最后,poly I:C诱导的疲劳被5-HT1A受体激动剂减轻,但未被5-HT2、5-HT3或多巴胺D3激动剂减轻。这些发现加在一起,表明大脑IFN-α和5-HTT表达的异常可能与poly I:C诱导的疲劳的神经元机制有关。

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