Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian 361021, China.
Evid Based Complement Alternat Med. 2013;2013:359682. doi: 10.1155/2013/359682. Epub 2013 Mar 17.
Background. Our previous study has demonstrated that nobiletin could reverse the behavioral alterations in stressed mice. However, the relation of its antidepressant-like action with neurotrophic molecular expression remains unknown. This study aimed to explore the antidepressant-like mechanism of nobiletin related to the neurotrophic system in rats exposed to chronic unpredictable mild stress (CUMS). Methods. Depressive-like anhedonia (assessed by sucrose preference) and serum corticosterone secretion were evaluated in the CUMS, followed by brain-derived neurotrophic factor (BDNF), its tropomyosin-related kinase receptor B (TrkB), and the downstream target synapsin I expressions in the hippocampus. Results. Anhedonia, which occurred within week 2, was rapidly ameliorated by nobiletin. While fluoxetine needed additional 2 weeks to improve the anhedonia. In addition, nobiletin administration for 5 weeks significantly ameliorated CUMS-induced increase in serum corticosterone levels. Furthermore, we also found that CUMS-induced deficits of hippocampal BDNF, TrkB, and synapsin I were ameliorated by nobiletin. Conclusions. Taken together, these findings suggest that nobiletin produces rapidly acting antidepressant-like responses in the CUMS and imply that BDNF-TrkB pathway may play an important role in the antidepressant-like effect of nobiletin.
我们之前的研究表明，川陈皮素可逆转应激小鼠的行为改变。然而，其抗抑郁样作用与神经营养分子表达的关系尚不清楚。本研究旨在探讨川陈皮素在慢性不可预测轻度应激（CUMS）大鼠中与神经营养系统相关的抗抑郁样机制。
在 CUMS 中评估抑郁样快感缺失（通过蔗糖偏好评估）和血清皮质酮分泌，然后评估海马脑源性神经营养因子（BDNF）、其原肌球蛋白相关激酶受体 B（TrkB）及其下游靶标突触素 I 的表达。
快感缺失在第 2 周内迅速得到改善，而氟西汀则需要额外的 2 周时间才能改善快感缺失。此外，川陈皮素治疗 5 周可显著改善 CUMS 引起的血清皮质酮水平升高。此外，我们还发现川陈皮素可改善 CUMS 诱导的海马 BDNF、TrkB 和突触素 I 的缺陷。
综上所述，这些发现表明川陈皮素在 CUMS 中产生快速抗抑郁样反应，并表明 BDNF-TrkB 通路可能在川陈皮素的抗抑郁样作用中发挥重要作用。
