Clock gene expression during chronic inflammation induced by infection with Trypanosoma brucei brucei in rats.

Clock gene expression during chronic inflammation induced by infection with Trypanosoma brucei brucei in rats.
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DOI:
10.1177/0748730409360963
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发表时间:
2010-04
影响因子:
3.5
通讯作者:
Block GD
Block GD
中科院分区:
生物学3区
文献类型:
--
作者:
Lundkvist GB;Sellix MT;Nygård M;Davis E;Straume M;Kristensson K;Block GD

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非洲昏睡病的特点是节律功能的改变。目前尚不清楚这种疾病是否会影响时钟基因的表达,时钟基因是节律产生的分子基础。我们利用布氏锥虫(TB Brucei)细胞外寄生虫引起的实验性昏睡病大鼠模型,研究其对Clock基因表达的影响。在感染布氏结核杆菌的PER1-Luc转基因大鼠脑垂体组织外植体中,PER1-Luc的表达周期明显缩短。在含有视交叉上核(SCN)的外植体中,21%的组织中PER1-LUC节律是平坦的。我们还用定量聚合酶链式反应检测了对照和感染大鼠的SCN、松果体和脾中PER1、CLOCK和BMal1mRNA的相对表达。布氏结核杆菌感染松果体后,松果体和脾组织中Clock和BMal1mRNA的表达均降低。感染大鼠的核心体温和运动活动都是周期性的;然而,在感染后的早期,我们观察到运动活动节律的幅度显著下降。此外,活动节律和体温节律都表现出规律性和健壮性降低。综上所述,尽管先前已经证明实验性锥虫感染会导致SCN神经元的功能紊乱,但只有21%的SCN外植体扰乱了PER1-LUC节律。然而,我们的数据显示,感染总体上改变了包括脑下垂体、松果体和脾在内的外周生物钟的分子时钟功能。
African sleeping sickness is characterized by alterations in rhythmic functions. It is not known if the disease affects the expression of clock genes, which are the molecular basis for rhythm generation. We used a chronic rat model of experimental sleeping sickness, caused by the extracellular parasite Trypanosoma brucei brucei (Tb brucei), to study the effects on clock gene expression. In tissue explants of pituitary glands from Period1-luciferase (Per1-luc) transgenic rats infected with Tb brucei, the period of Per1-luc expression was significantly shorter. In explants containing the suprachiasmatic nuclei (SCN), the Per1-luc rhythms were flat in 21% of the tissues. We also examined the relative expression of Per1, Clock, and Bmal1 mRNA in the SCN, pineal gland, and spleen from control and infected rats using qPCR. Both Clock and Bmal1 mRNA expression was reduced in the pineal gland and spleen following Tb brucei infection. Infected rats were periodic both in core body temperature and in locomotor activity; however, early after infection, we observed a significant decline in the amplitude of the locomotor activity rhythm. In addition, both activity and body temperature rhythms exhibited decreased regularity and “robustness.” In conclusion, although experimental trypanosome infection has previously been shown to cause functional disturbances in SCN neurons, only 21% of the SCN explants had disturbed Per1-luc rhythms. However, our data show that the infection overall alters molecular clock function in peripheral clocks including the pituitary gland, pineal gland, and spleen.
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