Katafuchi Toshihiko, Kondo Tetsuya, Take Sachiko, Yoshimura Megumu
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Ann N Y Acad Sci. 2006 Nov;1088:230-7. doi: 10.1196/annals.1366.020.
Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but also by the central nervous system (CNS). For example, it is generally known that the feeling of fatigue is greatly influenced by psychological aspects, such as motivation. However, little is known about the central mechanisms of fatigue. The clinical symptoms of chronic fatigue syndrome (CFS) are shown to include disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it has been demonstrated that cytokines produced in the brain play significant roles in neural-immune interactions through their various central actions, including hypothalamo-pituitary and sympathetic activation, as well as immunosuppression. In this article, using the immunologically induced fatigue model, which was achieved by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs, polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an involvement of brain interferon-alpha (IFN-alpha) and serotonin (5-HT) transporter (5-HTT) in the central mechanisms of fatigue. In the poly I:C-induced fatigue rats, expression of IFN-alpha and 5-HTT increased, while extracellular concentration of 5-HT in the medial prefrontal cortex decreased, probably on account of the enhanced expression of 5-HTT. Since the poly I:C-induced reduction of the running wheel activity was attenuated by a 5-HT(1A) receptor agonist, but not by 5-HT(2), 5-HT(3), or dopamine D(3) receptor agonists, it is suggested that the decrease in 5-HT actions on 5-HT(1A) receptors may at least partly contribute to the poly I:C-induced fatigue.
疲劳不仅由外周因素诱发，如肌肉疲劳，还由中枢神经系统（CNS）诱发。例如，众所周知，疲劳感会受到心理因素的极大影响，如动机。然而，关于疲劳的中枢机制却知之甚少。慢性疲劳综合征（CFS）的临床症状显示包括神经内分泌、自主神经和免疫系统的紊乱。另一方面，已经证明大脑中产生的细胞因子通过其各种中枢作用，包括下丘脑 - 垂体和交感神经激活以及免疫抑制，在神经 - 免疫相互作用中发挥重要作用。在本文中，我们使用通过腹腔内（i.p.）注射合成双链RNA（聚肌苷酸：聚胞苷酸，poly I:C）在大鼠中建立的免疫诱导疲劳模型，表明脑内干扰素 - α（IFN - α）和5 - 羟色胺（5 - HT）转运体（5 - HTT）参与了疲劳的中枢机制。在poly I:C诱导的疲劳大鼠中，IFN - α和5 - HTT的表达增加，而内侧前额叶皮质中5 - HT的细胞外浓度降低，这可能是由于5 - HTT表达增强所致。由于poly I:C诱导的跑步轮活动减少被5 - HT（1A）受体激动剂减弱，但未被5 - HT（2）、5 - HT（3）或多巴胺D（3）受体激动剂减弱，因此提示5 - HT对5 - HT（1A）受体作用的降低可能至少部分导致了poly I:C诱导的疲劳。
