Ryanodine receptors are involved in the improvement of depression-like behaviors through electroconvulsive shock in stressed mice.
Ryanodine receptors are involved in the improvement of depression-like behaviors through electroconvulsive shock in stressed mice.
复制标题
Ryanodine 受体通过应激小鼠的电休克来改善抑郁样行为。
DOI：
10.1016/j.brs.2020.11.001
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发表时间：
2021
影响因子：
7.7
通讯作者：
Miyamoto O
中科院分区：
文献类型：
--
作者：
91.Nakamura-Maruyama E;Kai R;Himi N;Okabe N;Narita K;Miyazaki T;Aoki S;Miyamoto O
研究背景电休克疗法（Electroconvulsive therapy，ECT）是治疗抑郁症的有效方法。然而，ECT的抗抑郁作用的机制仍不清楚。抑郁症患者表现出异常的钙动力学。细胞内Ca ~（2+）信号通路的早期阶段涉及Ca ~（2+）通过Ca ~（2+）释放通道从内质网（ER）释放Ca ~（2+）。本研究旨在探讨电休克（electroconvulsive shock，ECS）对大鼠海马Ryanodine受体（ryanodine receptor，RyRs）和1，4，5-三磷酸肌醇受体（inositol 1，4，5-trisphosphate receptor，IP 3Rs）的影响。他们的抑郁样状态进行了行为学和组织学评估强迫游泳试验，新奇抑制喂养试验，并通过评估海马齿状回的神经发生，分别。A RyRs阻滞剂，丹曲林，前ECS，抑郁样条件的变化进行了examined.ResultsThe蛋白表达的RyR 1和RyR 3的抑郁样症状的小鼠模型的海马中显着增加。由于ECS应用，抑郁样症状减少，这种增加减弱。然而，预注射与丹曲林降低ECS.ConclusionsA抑郁样状态和抑郁样症状的RyRs抑制剂的加重RyRs表达的显着增加可能是由RyRs功能障碍引起的，这表明RyRs的过度表达是一种代偿作用。通过ECS使RyRs表达水平正常化表明ECT通过RyRs使Ca 2+释放正常化。因此，RyRs功能的正常化可能在ECT的治疗效果中起重要作用。
BackgroundElectroconvulsive 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.ObjectiveWe 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).MethodsA 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.ResultsThe 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.ConclusionsA 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.