Department of General Medicine, Kanazawa Medical University, Ishikawa 920–0293, Japan.
Biol Pharm Bull. 2011;34(3):354-9. doi: 10.1248/bpb.34.354.
Neuroimaging evidence showed structural and/or functional abnormalities existing in the central nervous system, especially the hippocampus, in chronic fatigue syndrome (CFS) patients. However, its pathophysiologic mechanisms are unclear in part due to the lack of an applicable animal model. We established a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy. Thereafter, resveratrol, a polyphenolic activator of sirtuin 1, was used for treatment in this model. Daily running activity was increased by more than 20%, and the hippocampus was enlarged after 4-week resveratrol therapy. Furthermore, resveratrol inhibited neuronal apoptosis and expression of hippocampal acetylated p53 in the fatigue mice. Resveratrol also improved neurogenesis and expression of brain-derived neurotrophic factor mRNA in the hippocampus. We concluded that repeated injection of B. abortus antigen could induce hypoactivity and hippocampal atrophy in mice. Resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis.
神经影像学证据表明，慢性疲劳综合征（CFS）患者的中枢神经系统（尤其是海马体）存在结构和/或功能异常。然而，其病理生理机制尚不清楚，部分原因是缺乏适用的动物模型。我们通过向小鼠重复注射布鲁氏菌抗原建立了慢性疲劳小鼠模型，该模型表现为每日跑步活动减少和海马体萎缩。此后，白藜芦醇作为 SIRT1 的一种多酚激活剂，用于该模型的治疗。经过 4 周的白藜芦醇治疗，每日跑步活动增加了 20%以上，海马体增大。此外，白藜芦醇抑制了疲劳小鼠的神经元凋亡和海马乙酰化 p53 的表达。白藜芦醇还改善了海马体中的神经发生和脑源性神经营养因子 mRNA 的表达。我们得出结论，反复注射布鲁氏菌抗原可导致小鼠活动减少和海马体萎缩。白藜芦醇可能通过抑制凋亡和促进神经发生来有效改善疲劳症状和扩大萎缩的海马体。
