Yamashita Masatoshi
Graduate School of Advanced Integrated Studies in Human Survivability, Kyoto University, Kyoto, Japan.
Int J Tryptophan Res. 2020 Jun 29;13:1178646920936279. doi: 10.1177/1178646920936279. eCollection 2020.
Central fatigue leads to reduced ability to perform mental tasks, disrupted social life, and impaired brain functions from childhood to old age. Regarding the neurochemical mechanism, neuroactive tryptophan metabolites are thought to play key roles in central fatigue. Previous studies have supported the "tryptophan-serotonin enhancement hypothesis" in which tryptophan uptake into extensive brain regions enhances serotonin production in the rat model of exercise-induced fatigue. However, serotonin was transiently released after 30 minutes of treadmill running to exhaustion, but this did not reflect the duration of fatigue. In addition, as the vast majority of tryptophan is metabolized along the kynurenine pathway, possible involvement of the tryptophan-kynurenine pathway in the mechanism of central fatigue induction has been pointed out. More recently, our study demonstrated that uptake of tryptophan and kynurenine derived from the peripheral circulation into the brain enhances kynurenic acid production in rat brain in sleep deprivation-induced central fatigue, but without change in serotonin activity. In particular, dynamic change in glial-neuronal interactive processes within the hypothalamus-hippocampal circuit causes central fatigue. Furthermore, increased tryptophan-kynurenine pathway activity in this circuit causes reduced memory function. This indicates a major potential role for the endogenous tryptophan-kynurenine pathway in central fatigue, which supports the "tryptophan-kynurenine enhancement hypothesis." Here, we review research on the basic neuronal mechanism underlying central fatigue induced by neuroactive tryptophan metabolites. Notably, these basic findings could contribute to our understanding of latent mental problems associated with central fatigue.
中枢性疲劳会导致执行脑力任务的能力下降、社交生活紊乱，且从童年到老年都会损害脑功能。关于神经化学机制，神经活性色氨酸代谢产物被认为在中枢性疲劳中起关键作用。先前的研究支持“色氨酸 - 血清素增强假说”，即在运动诱导疲劳的大鼠模型中，色氨酸进入广泛脑区会增强血清素的产生。然而，在跑步机上跑至精疲力竭30分钟后血清素会短暂释放，但这并未反映疲劳的持续时间。此外，由于绝大多数色氨酸是沿犬尿氨酸途径代谢的，因此有人指出色氨酸 - 犬尿氨酸途径可能参与中枢性疲劳的诱导机制。最近，我们的研究表明，在睡眠剥夺诱导的中枢性疲劳中，源自外周循环的色氨酸和犬尿氨酸进入大脑会增强大鼠脑中犬尿酸的产生，但血清素活性没有变化。特别是，下丘脑 - 海马回路内神经胶质 - 神经元相互作用过程的动态变化会导致中枢性疲劳。此外，该回路中色氨酸 - 犬尿氨酸途径活性增加会导致记忆功能下降。这表明内源性色氨酸 - 犬尿氨酸途径在中枢性疲劳中具有重要潜在作用，这支持了“色氨酸 - 犬尿氨酸增强假说”。在此，我们综述了关于神经活性色氨酸代谢产物诱导中枢性疲劳的基本神经元机制的研究。值得注意的是，这些基本发现可能有助于我们理解与中枢性疲劳相关的潜在心理问题。
