Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan.
Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr 3;50:37-43. doi: 10.1016/j.pnpbp.2013.11.012. Epub 2013 Dec 4.
The putative antidepressive mechanisms of a series of electroconvulsive seizures (ECS) are the following: 1) downregulation of monoaminergic receptor expression in several brain regions, 2) upregulation of the expression of brain-derived neurotrophic factor (BDNF), and 3) increased neurogenesis in the hippocampus. In this study, we used Western blot techniques to present another mechanism in which ECS enhances the autophagy signaling that is involved in the machinery related to synaptic and neural plasticity. Antibodies for conjugated Atg5-Atg12 (58kD) and cleaved light chain protein 3-II (LC3-II; 14 kD) were used to detect autophagy signals. An antibody for cleaved caspase-3 (17 kD) was used to detect alterations in apoptotic signals. Mature BDNF (14kD) expression in the hippocampus was evaluated in order to qualify the effectiveness of the ECS or stress-loading treatment. While significantly increased autophagy signals and no increases in apoptotic signals were detected in the ECS-treated rat hippocampus, the reverse (increased apoptotic signals and no altered autophagy signals) was observed in stressed rat hippocampus. No neuronal cell loss but new mossy fiber sprouting has been reported to accompany multiple ECS treatments, and recent studies have revealed that autophagy processes regulate the number of specific neurotransmitter receptors and the plasticity of synaptic components. The present study illustrated the neuroplastic and neurotrophic profiles of ECS and the neurotoxic impact of severe stress loading on hippocampal regions. This is the first report to demonstrate increased autophagy signals in ECS-treated rat hippocampus and no alterations in autophagy signals in stress-loaded rat hippocampus.
一系列电惊厥（ECS）的假定抗抑郁机制如下：1）下调几种脑区的单胺能受体表达，2）上调脑源性神经营养因子（BDNF）的表达，以及 3）海马体中的神经发生增加。在这项研究中，我们使用 Western blot 技术提出了另一种机制，即 ECS 增强了自噬信号，该信号涉及与突触和神经可塑性相关的机制。用于检测自噬信号的抗体为共轭 Atg5-Atg12（58kD）和裂解的轻链蛋白 3-II（LC3-II；14 kD）。用于检测凋亡信号改变的抗体为裂解的半胱天冬酶-3（17 kD）。评估海马体中成熟 BDNF（14kD）的表达，以确定 ECS 或应激加载处理的有效性。在 ECS 处理的大鼠海马体中检测到自噬信号显著增加而凋亡信号没有增加，而在应激大鼠海马体中则观察到相反的情况（凋亡信号增加而自噬信号没有改变）。据报道，多次 ECS 治疗伴随着神经元细胞丢失，但新的苔藓纤维发芽，最近的研究表明自噬过程调节特定神经递质受体的数量和突触成分的可塑性。本研究说明了 ECS 的神经可塑性和神经营养特性以及严重应激负荷对海马区的神经毒性影响。这是第一项表明 ECS 处理的大鼠海马体中自噬信号增加而应激负荷的大鼠海马体中自噬信号没有改变的报告。
