Core Center for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Int J Neuropsychopharmacol. 2020 Jul 29;23(7):446-458. doi: 10.1093/ijnp/pyaa021.
Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression used in the clinic. Its mechanism of therapeutic action remains uncertain. Previous studies have focused on documenting neuroplasticity in the early phase following electroconvulsive seizures (ECS), an animal model of ECT. Here, we investigate whether changes in synaptic plasticity and nonneuronal plasticity (vascular and mitochondria) are sustained 3 months after repeated ECS trials.
ECS or sham treatment was given daily for 1 day or 10 days to a genetic animal model of depression: the Flinders Sensitive and Resistant Line rats. Stereological principles were employed to quantify numbers of synapses and mitochondria as well as length of microvessels in the hippocampus 24 hours after a single ECS. Three months after 10 ECS treatments (1 per day for 10 days) and sham-treatment, brain-derived neurotrophic factor and vascular endothelial growth factor protein levels were quantified with immunohistochemistry.
A single ECS treatment significantly increased the volume of hippocampal CA1-stratum radiatum, the total length of microvessels, mitochondria number, and synapse number. Observed changes were sustained as shown in the multiple ECS treatment group analyzed 3 months after the last of 10 ECS treatments.
A single ECS caused rapid effects of synaptic plasticity and nonneuronal plasticity, while repeated ECS induced long-lasting changes in the efficacy of synaptic plasticity and nonneuronal plasticity at least up to 3 months after ECS.
电抽搐疗法(ECT)是一种在临床上用于治疗抑郁症的高效、快速作用的治疗方法。其治疗作用机制仍不确定。先前的研究主要集中在记录电抽搐发作(ECS)后的早期神经可塑性上,这是 ECT 的动物模型。在这里,我们研究了在重复 ECS 试验 3 个月后,突触可塑性和非神经元可塑性(血管和线粒体)是否发生变化。
对抑郁症的遗传动物模型:弗林德斯敏感和抗性线大鼠进行每日 ECS 或假处理,持续 1 天或 10 天。立体学原理用于在单次 ECS 后 24 小时定量海马中的突触和线粒体数量以及微血管长度。在 10 次 ECS 治疗(每天 1 次,共 10 天)和假治疗 3 个月后,用免疫组织化学法定量脑源性神经营养因子和血管内皮生长因子蛋白水平。
单次 ECS 治疗显著增加了海马 CA1 放射状层的体积、微血管总长度、线粒体数量和突触数量。在最后一次 ECS 治疗后 3 个月分析的多次 ECS 治疗组中观察到了持续的变化。
单次 ECS 引起了突触可塑性和非神经元可塑性的快速变化,而重复 ECS 至少在 ECS 后 3 个月诱导了突触可塑性和非神经元可塑性的长期变化。