Altered neuronal activity rhythm and glutamate receptor expression in the suprachiasmatic nuclei of Trypanosoma brucei-infected rats
Altered neuronal activity rhythm and glutamate receptor expression in the suprachiasmatic nuclei of Trypanosoma brucei-infected rats
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DOI：
10.1097/00005072-199801000-00004
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发表时间：
1998-01-01
影响因子：
3.2
通讯作者：
Kristensson, K
中科院分区：
文献类型：
--
作者：
Lundkvist, GB;CHristenson, J;Kristensson, K
寄生虫布氏锥虫会引起非洲锥虫病（昏睡病），这是一种严重的神经精神疾病，伴有明显的睡眠-觉醒交替障碍。脑损伤的部位尚不明确。目前的实验研究主要集中在下丘脑视交叉上核，它在哺乳动物大脑中发挥生物钟的作用，控制内源性节律。在感染锥虫的大鼠的切片中分析了这些神经元的电生理学特性。显示昼夜节律振荡的神经元自发活动在受感染的动物中显着改变，表现出放电率降低和昼夜节律峰值相位提前。直接视网膜纤维在昼夜节律起搏器的牵引中起关键作用，在体内眼内注射示踪剂后，在受感染动物的视交叉上核中显示出正常的密度和分布。在突触后水平，免疫组织化学和蛋白质印迹显示，在受感染大鼠的视交叉上核中，控制视网膜传入的谷氨酸 AMPA GluR2/3 和 NMDAR1 受体亚基的表达选择性降低。这些数据揭示了非洲锥虫病生物钟神经元功能的损害，并可能有助于揭示内源性节律紊乱背后的功能和分子机制。
The parasites Trypanosoma brucei cause African trypanosomiasis (sleeping sickness), a severe neuropsychiatric disease with marked disturbances of sleep-wake alternation. The sites of brain lesions are not well characterized. The present experimental investigation is focused on the hypothalamic suprachiasmatic nuclei, which play a role of a biological clock entraining endogenous rhythms in the mammalian brain. The electrophysiological properties of these neurons were analyzed in slice preparations from trypanosome-infected rats The neuronal spontaneous activity, which shows a circadian oscillation, was markedly altered in the infected animals, displaying a reduced firing rate and phase advance of its circadian peak. The direct retinal fibers, which play a pivotal role in entrainment of the circadian pacemaker, displayed a normal density and distribution in the suprachiasmatic nuclei of infected animals after intraocular tracer injections in vivo. At the postsynaptic level, immunohistochemistry and Western blotting revealed in the suprachiasmatic nuclei of infected rats a selective decrease of the expression of glutamate AMPA GluR2/3 and NMDAR1 receptor subunits that gate retinal afferents. These data disclose an impairment of the neuronal functions in the biological clock in African trypanosomiasis, and may serve to unravel functional and molecular mechanisms behind endogenous rhythm disturbances.