BACKGROUND It is uncertain how electroconvulsive therapy-induced generalized seizures exert their potent therapeutic effects on various neuropsychiatric disorders. Adenosine monophosphate-activated protein kinase (AMPK) plays a major role in maintaining metabolic homeostasis and activates autophagic processes via unc-51-like kinase (ULK1). Evidence supports the involvement of autophagy system in the action mechanisms of antidepressants and antipsychotics. The effect of electroconvulsive therapy on autophagy-related signaling requires further clarification. METHODS The effect of electroconvulsive seizure on autophagy and its association with the AMPK signaling pathway were investigated in the rat frontal cortex. Electroconvulsive seizure was provided once per day for 10 days (E10X), and compound C or 3-methyadenine was administered through an intracerebroventricular cannula. Molecular changes were analyzed with immunoblot, immunohistochemistry, and transmission electron microscopy analyses. RESULTS E10X increased p-Thr172-AMPKα immunoreactivity in rat frontal cortex neurons. E10X increased phosphorylation of upstream effectors of AMPK, such as LKB1, CaMKK, and TAK1, and of its substrates, ACC, HMGR, and GABABR2. E10X also increased p-Ser317-ULK1 immunoreactivity. At the same time, LC3-II and ATG5-ATG12 conjugate immunoreactivity increased, indicating activation of autophagy. An intracerebroventricular injection of the AMPK inhibitor compound C attenuated the electroconvulsive seizure-induced increase in ULK1 phosphorylation as well as the protein levels of LC3-II and Atg5-Atg12 conjugate. Transmission electron microscopy clearly showed an increased number of autophagosomes in the rat frontal cortex after E10X, which was reduced by intracerebroventricular treatment with the autophagy inhibitor 3-methyadenine and compound C. CONCLUSIONS Repeated electroconvulsive seizure treatments activated in vivo autophagy in the rat frontal cortex through the AMPK signaling pathway.

中文翻译：

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电惊厥性癫痫发作通过激活大鼠额叶皮质中的AMPK信号通路来诱导自噬。

背景技术尚不确定电惊厥治疗引起的全身性癫痫如何对各种神经精神疾病发挥有效的治疗作用。腺苷单磷酸激活蛋白激酶（AMPK）在维持代谢稳态中起主要作用，并通过unc-51-like激酶（ULK1）激活自噬过程。证据支持自噬系统参与抗抑郁药和抗精神病药的作用机制。电痉挛疗法对自噬相关信号的作用需要进一步阐明。方法在大鼠额叶皮层研究电惊厥对自噬的影响及其与AMPK信号通路的关系。每天提供一次电惊厥发作，持续10天（E10X），通过脑室内套管施用化合物C或3-甲基腺嘌呤。用免疫印迹，免疫组织化学和透射电子显微镜分析法分析分子变化。结果E10X增加了大鼠额叶皮质神经元的p-Thr172-AMPKα免疫反应性。E10X增加了AMPK上游效应子（如LKB1，CaMKK和TAK1）及其底物ACC，HMGR和GABABR2的磷酸化。E10X还增加了p-Ser317-ULK1免疫反应性。同时，LC3-II和ATG5-ATG12缀合物的免疫反应性增加，表明自噬被激活。脑室内注射AMPK抑制剂化合物C减弱了电惊厥引起的ULK1磷酸化水平的增加以及LC3-II和Atg5-Atg12偶联物的蛋白水平。