■本研究旨在确定电针(EA)治疗对中风后抑郁(PSD)的影响,并探讨大麻素受体1(CB1R)介导的线粒体生物发生是否解释了EA的治疗效果。
■在从双侧颈总动脉闭塞手术恢复7天后,通过连续14天的慢性不可预测的应激手术诱导PSD小鼠模型。从BCCAO手术后第7天起连续14天进行EA治疗或假刺激。受试者的PSD样行为通过开放场测试进行测试,蔗糖偏好测试,新奇抑制喂养测试,尾部悬挂试验,强迫游泳测试,使用Y迷宫和新颖性物体识别测试检查受试者的认知功能。此外,CB1R的水平,线粒体生物发生相关蛋白(核转录因子1,NRF1;线粒体转录因子A,TFAM),与线粒体功能相关的蛋白质(细胞色素C,CytoC;AIF,COXIV),并测量线粒体DNA。为了阐明CB1R在EA治疗中的作用,在EA处理之前,将CB1R拮抗剂AM251和CB1R-shRNA给予小鼠。同样,受试者类似抑郁的行为,认知功能,线粒体功能,PSD程序后检查线粒体生物发生。
■研究表明,EA成功改善了类似抑郁的行为,改善认知功能障碍,并上调CB1R,NRF1和TFAM表达式。然而,补充AM251和CB1R-shRNA阻断了EA产生的抗抑郁样作用,EA未能改善认知功能障碍,上调CB1R蛋白表达,增加线粒体功能和生物发生。
■总之,这些结果表明EA改善了小鼠的PSD样行为,改善PSD后的认知功能障碍,并通过激活CB1R促进线粒体生物发生,EA类抗抑郁作用治疗PSD的新机制。
UNASSIGNED: This study aimed to identify the effect of electroacupuncture (EA) treatment on post-stroke depression (PSD) and explore whether cannabinoid receptor 1 (CB1R)-mediated mitochondrial biogenesis accounts for the treatment effect of EA.
UNASSIGNED: The PSD mouse model was induced by a consecutive 14-day chronic unpredictable stress operation after 7 days of recovery from the bilateral common carotid artery occlusion surgery. Either EA treatment or sham stimulation was performed for 14 consecutive days from Day 7 after the BCCAO operation. Subjects\' PSD-like behaviors were tested via open field test, sucrose preference test, novelty suppressed feeding test, tail suspension test, and forced swim test, and subjects\' cognitive function was examined using Y-maze and novelty object recognition test. In addition, the levels of CB1R, mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), proteins related to mitochondrial function (Cytochrome C, Cyto C; AIF, COX IV), and mitochondrial DNA were measured. To elucidate the role of CB1R in EA treatment, CB1R antagonists AM251 and CB1R-shRNA were given to mice before EA treatment. Likewise, subjects\' depressive-like behaviors, cognitive function, mitochondrial function, and mitochondrial biogenesis were examined after the PSD procedure.
UNASSIGNED: It has been showed that EA successfully ameliorated depressive-like behaviors, improved cognitive dysfunctions, and upregulated CB1R, NRF1 and TFAM expressions. However, the supplementation of AM251 and CB1R-shRNA blocked the antidepressant-like effects generated by EA, and EA failed to improve cognitive dysfunction, upregulate CB1R protein expression, and increase mitochondrial function and biogenesis.
UNASSIGNED: Altogether, these results indicated that EA ameliorated PSD-like behaviors in mice, improved cognitive dysfunctions after PSD, and promoted mitochondrial biogenesis by activating CB1R, a novel mechanism underlying EA\'s antidepressant-like effects in treating PSD.