PDF(Pubmed)
Abstract：
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a significant medical challenge, with no indisputable pathophysiological mechanism identified to date.
Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models.
High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown.
Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.
Based on clinical clues, we hypothesized that 5-hydroxytryptamine (5-HT) hyperactivation is implicated in the pathogenic causes of ME/CFS and the associated symptoms. We experimentally evaluated this hypothesis in a series of mouse models.
High-dose selective serotonin reuptake inhibitor (SSRI) treatment induced intra- and extracellular serotonin spillover in the dorsal raphe nuclei of mice. This condition resulted in severe fatigue (rota-rod, fatigue rotating wheel and home-cage activity tests) and ME/CFS-associated symptoms (nest building, plantar and open field test), along with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis response to exercise challenge. These ME/CFS-like features induced by excess serotonin were additionally verified using both a 5-HT synthesis inhibitor and viral vector for Htr1a (5-HT1A receptor) gene knockdown.
Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches.
摘要：
目的：肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一个重大的医学挑战，迄今为止，尚无无可争议的病理生理机制。
方法：根据临床线索，我们假设5-羟色胺(5-HT)过度激活与ME/CFS的致病原因和相关症状有关.我们在一系列小鼠模型中实验评估了这一假设。
结果：高剂量选择性5-羟色胺再摄取抑制剂（SSRI）治疗可诱导小鼠背中缝核内和细胞外5-羟色胺溢出。这种情况导致严重疲劳(rota-rota，疲劳旋转轮和家笼活动测试)和ME/CFS相关症状(筑巢，足底和露地试验)，伴随下丘脑-垂体-肾上腺（HPA）轴对运动挑战的反应功能障碍。使用5-HT合成抑制剂和Htr1a（5-HT1A受体）基因敲低的病毒载体，进一步验证了由过量5-羟色胺诱导的这些ME/CFS样特征。
结论：我们的发现支持5-强能过度活动参与ME/CFS的病理生理学。这种模拟ME/CFS的动物模型将有助于理解ME/CFS生物学及其治疗方法。
方法：根据临床线索，我们假设5-羟色胺(5-HT)过度激活与ME/CFS的致病原因和相关症状有关.我们在一系列小鼠模型中实验评估了这一假设。
结果：高剂量选择性5-羟色胺再摄取抑制剂（SSRI）治疗可诱导小鼠背中缝核内和细胞外5-羟色胺溢出。这种情况导致严重疲劳(rota-rota，疲劳旋转轮和家笼活动测试)和ME/CFS相关症状(筑巢，足底和露地试验)，伴随下丘脑-垂体-肾上腺（HPA）轴对运动挑战的反应功能障碍。使用5-HT合成抑制剂和Htr1a（5-HT1A受体）基因敲低的病毒载体，进一步验证了由过量5-羟色胺诱导的这些ME/CFS样特征。
结论：我们的发现支持5-强能过度活动参与ME/CFS的病理生理学。这种模拟ME/CFS的动物模型将有助于理解ME/CFS生物学及其治疗方法。
