Electroacupuncture treatment ameliorates depressive-like behavior and cognitive dysfunction via CB1R dependent mitochondria biogenesis after experimental global cerebral ischemic stroke

• Published in: Frontiers in cellular neuroscience Vol. 17; p. 1135227
• Main Authors: Hu, Guangtao, Zhou, Cuihong, Wang, Jin, Ma, Xinxu, Ma, Hongzhe, Yu, Huan, Peng, Zhengwu, Huang, Jing, Cai, Min
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 05.04.2023; Frontiers Media S.A
• Subjects: Acupuncture; Animal cognition; Antidepressants; Apoptosis-inducing factor; Behavior; Biosynthesis; Brain research; Cannabinoid CB1 receptors; cannabinoid receptor 1; Carotid artery; Cerebral blood flow; cerebral ischemia/reperfusion; Cognitive ability; Cytochrome c; depressive-like behaviors; Electroacupuncture; Emotional disorders; Ischemia; Kinases; Medical research; Mental depression; Mitochondria; mitochondrial biogenesis; Mitochondrial DNA; mitochondrial function; Mood disorders; Neuroscience; Novelty; Open-field behavior; Pattern recognition; Proteins; Stroke; Sucrose; Veins & arteries; China; mitochondrial function; cerebral ischemia/reperfusion; cannabinoid receptor 1; electroacupuncture; cognitive dysfunction; mitochondrial biogenesis; depressive-like behaviors
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2023.1135227

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. 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. 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. 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.