Kim Se Hyun, Park Hong Geun, Jeong Seong Hoon, Kang Ung Gu, Ahn Yong Min, Kim Yong Sik
Department of Neuropsychiatry, Dongguk University International Hospital, Dongguk University Medical School, Goyang, Republic of Korea.
Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Psychiatry Investig. 2018 Jul;15(7):717-726. doi: 10.30773/pi.2018.01.18.2. Epub 2018 Jun 28.
Electroconvulsive therapy (ECT) is the most effective treatment for mood disorders. Accumulating evidence has suggested the important role of circadian genes in mood disorders. However, the effects of ECT on circadian genes have not been systemically investigated.
We examined the expression and daily oscillation of major circadian genes in the rat frontal cortex after electroconvulsive seizure (ECS).
Firstly, mRNA and protein level were investigated at 24 hr after single ECS (E1X) and repeated ECS treatements for 10 days (E10X), which showed more remarkable changes after E10X than E1X. mRNA expression of Rorα, Bmal1, Clock, Per1, and Cry1 was decreased, while Rev-erbα expression was increased at 24 hr after E10X compared to sham. The proteins showed similar pattern of changes. Next, the effects on oscillation and rhythm properties (mesor, amplitude, and acrophase) were examined, which also showed more prominent changes after E10X than E1X. After E10X, mesor of Rorα, Bmal1, and Cry1 was reduced, and that of Rev-erbα was increased. Five genes, Rev-erbα, Bmal1, Per1, Per2, and Cry2, showed earlier acrophase after E10X.
The findings suggest that repeated ECS induces reduced expression and phase advance of major circadian genes in the in vivo rat frontal cortex.
电休克治疗(ECT)是治疗情绪障碍最有效的方法。越来越多的证据表明昼夜节律基因在情绪障碍中起重要作用。然而,ECT对昼夜节律基因的影响尚未得到系统研究。
我们检测了电惊厥发作(ECS)后大鼠额叶皮质中主要昼夜节律基因的表达和每日振荡情况。
首先,在单次ECS(E1X)和重复ECS治疗10天(E10X)后24小时检测mRNA和蛋白质水平,结果显示E10X后的变化比E1X更显著。与假手术组相比,E10X后24小时,Rorα、Bmal1、Clock、Per1和Cry1的mRNA表达降低,而Rev-erbα表达增加。蛋白质显示出类似的变化模式。其次,检测对振荡和节律特性(中值、振幅和峰相位)的影响,结果也显示E10X后的变化比E1X更显著。E10X后,Rorα、Bmal1和Cry1的中值降低,Rev-erbα的中值增加。五个基因,Rev-erbα、Bmal1、Per1、Per2和Cry2,在E10X后显示出更早的峰相位。
研究结果表明,重复ECS可导致体内大鼠额叶皮质中主要昼夜节律基因的表达降低和相位提前。