BACKGROUND Electroconvulsive therapy (ECT) is effective for treating depression. However, the mechanisms underlying the antidepressant effects of ECT remain unknown. Depressed patients exhibit abnormal Ca2+ kinetics. Early stages of the intracellular Ca2+ signaling pathway involve the release of Ca2+ from the endoplasmic reticulum (ER) via Ca2+ release channels. OBJECTIVE We considered that depression may be improved via ECT-induced normalization of intracellular Ca2+ regulation through the Ca2+ release channels. The current study aimed to investigate the effects of ECT on two Ca2+ release channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). METHODS A mouse depression-like model subjected to water immersion with restraint stress was administered electroconvulsive shock (ECS) therapy. Their depression-like status was behaviorally and histologically assessed using forced swimming tests, novelty-suppressed feeding tests, and by evaluating neurogenesis in the hippocampal dentate gyrus, respectively. A RyRs blocker, dantrolene, was administered prior to ECS, and the changes in depression-like conditions were examined. RESULTS The protein expressions of RyR1 and RyR3 significantly increased in the hippocampus of the mouse model with depression-like symptoms. This increase was attenuated as depression-like symptoms were reduced due to ECS application. However, pre-injection with dantrolene reduced the antidepressant effects of ECS. CONCLUSIONS A significant increase in RyRs expression in a depression-like state and exacerbation of depression-like symptoms by RyRs inhibitors may be caused by RyRs dysfunction, suggesting overexpression of RyRs is a compensatory effect. Normalization of RyRs expression levels by ECS suggests that ECT normalizes the Ca2+ release via RyRs. Thus, normalizing the function of RyRs may play an important role in the therapeutic effect of ECT.

中文翻译：

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Ryanodine 受体通过应激小鼠的电休克改善抑郁样行为

背景电惊厥疗法(ECT)对治疗抑郁症是有效的。然而，ECT 抗抑郁作用的潜在机制仍然未知。抑郁症患者表现出异常的 Ca2+ 动力学。细胞内 Ca2+ 信号通路的早期阶段涉及通过 Ca2+ 释放通道从内质网 (ER) 释放 Ca2+。目的 我们认为可以通过 ECT 诱导的细胞内 Ca2+ 调节通过 Ca2+ 释放通道的正常化来改善抑郁症。目前的研究旨在研究 ECT 对两个 Ca2+ 释放通道、兰尼碱受体 (RyRs) 和肌醇 1,4,5-三磷酸受体 (IP3Rs) 的影响。方法 对小鼠抑郁样模型进行电休克 (ECS) 治疗。他们的抑郁样状态分别使用强迫游泳测试、新奇抑制喂养测试和评估海马齿状回的神经发生在行为和组织学上进行评估。在 ECS 之前给予 RyRs 阻滞剂丹曲林，并检查抑郁样病症的变化。结果抑郁样症状小鼠模型海马区RyR1和RyR3蛋白表达显着升高。由于应用 ECS 减少了类似抑郁症的症状，因此这种增加有所减弱。然而，预先注射丹曲林会降低 ECS 的抗抑郁作用。结论 抑郁样状态下 RyRs 表达显着增加和 RyRs 抑制剂加重抑郁样症状可能是由 RyRs 功能障碍引起的，表明 RyRs 的过度表达是一种补偿作用。ECS 对 RyRs 表达水平的标准化表明 ECT 通过 RyRs 使 Ca2+ 释放正常化。因此，使 RyRs 的功能正常化可能在 ECT 的治疗效果中发挥重要作用。