Li Bingjin, Suemaru Katsuya, Kitamura Yoshihisa, Cui Ranji, Gomita Yutaka, Araki Hiroaki
Department of Clinical Pharmacology and Pharmacy, Brain Science, Ehime University Graduate School of Medicine, Ehime University Hospital, Japan.
Yakugaku Zasshi. 2007 Apr;127(4):735-42. doi: 10.1248/yakushi.127.735.
In recent years, depression studies have focused on morphological changes associated with depression. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that plays an important role in the morphological changes associated with depression and the mechanisms of antidepressants. On the other hand, hyperfunction of the hypothalamic-pituitary-adrenal axis has been link to pathophysiology of depression. In our previous studies, ACTH-treated rats served as a valuable animal model of tricyclic antidepressant-resistant depressive conditions. However, few neuroanatomic studies have been done. In the present study, we investigated mechanisms underling ACTH-treated rat serving an imipramine treatment-resistant depression model using c-Fos as a marker. The c-Fos immunohistochemical study indicated that the medial prefrontal cortex is an action site of imipramine in ACTH-treated rats. Electroconvulsive therapy is considered an effective treatment for treatment-resistant depression. However, the mechanisms causing treatment-resistant depressive conditions are unknown. We investigated the effect of repeated electrical convulsive shock (ECS)-treatment using the forced swim test, a screening method for antidepressant-like activity, and hippocampal BDNF protein levels in ACTH-treated rats. Findings showed that repeated ECS treatment decreased the immobility time during forced swim test. Furthermore, the ECS treatment also markedly increased the hippocampal BDNF levels in the rat tricyclic antidepressant-resistant depression model. In addition, the repeated ECS treatment showed long-lasting effects on forced swim test and increased of hippocampal BDNF levels in normal rats. These findings suggest that BDNF plays a key role in the antidepressant-like effect of ECS and that increased BDNF may be involved in promoting the long-lasting effect.
近年来，抑郁症研究主要聚焦于与抑郁症相关的形态学变化。脑源性神经营养因子（BDNF）是一种神经营养因子，在与抑郁症相关的形态学变化及抗抑郁药作用机制中发挥着重要作用。另一方面，下丘脑 - 垂体 - 肾上腺轴功能亢进已被认为与抑郁症的病理生理学相关。在我们之前的研究中，促肾上腺皮质激素（ACTH）处理的大鼠是三环类抗抑郁药耐药性抑郁状态的一种有价值的动物模型。然而，相关的神经解剖学研究较少。在本研究中，我们以c - Fos作为标志物，研究了ACTH处理的大鼠作为丙咪嗪治疗耐药性抑郁症模型的潜在机制。c - Fos免疫组化研究表明，内侧前额叶皮质是丙咪嗪在ACTH处理大鼠中的作用位点。电休克治疗被认为是治疗耐药性抑郁症的一种有效方法。然而，导致治疗耐药性抑郁状态的机制尚不清楚。我们使用强迫游泳试验（一种抗抑郁样活性的筛选方法）和ACTH处理大鼠海马中的BDNF蛋白水平，研究了重复电惊厥休克（ECS）治疗的效果。结果显示，重复ECS治疗可减少强迫游泳试验中的不动时间。此外，ECS治疗还显著提高了大鼠三环类抗抑郁药耐药性抑郁症模型海马中的BDNF水平。此外，重复ECS治疗对强迫游泳试验有持久影响，并提高了正常大鼠海马中的BDNF水平。这些发现表明，BDNF在ECS的抗抑郁样作用中起关键作用，BDNF水平升高可能参与促进这种持久作用。
