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

Abstract

IntroductionThis 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.MethodsThe 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.ResultsIt 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.ConclusionAltogether, 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.

Evaluation of electroacupuncture as a non-pharmacological therapy for astrocytic structural aberrations and behavioral deficits in a post-ischemic depression model in mice

“…Global cerebral ischemia (GCI) is a complex disorder that results from a wide range of pathologic events, including asphyxia, arrhythmia, cardiac arrest, and shock ( Neumann et al, 2013 ; Farajdokht et al, 2022 ). Due to the susceptibility of regions such as the hippocampus and cortex to ischemic insults, GCI is commonly accompanied by psychiatric disorders ( Hu et al, 2023 ). However, from an etiological standpoint, the physical and psychological stress caused by movement restriction and high dependency on caregivers may lead to intense negative emotions in subjects ( Farajdokht et al, 2022 ).…”

“…Besides, almost all antidepressants [selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors, and monoamine oxidase inhibitors] are associated with increased risks of adverse outcomes, including mortality, suicide, hemorrhagic complications, bone fractures, and seizures ( Li et al, 2022 ), and patients may exhibit treatment-refractory response and poor adherence to antidepressant drugs. Increasing attention has been paid to the application of EA for alleviating depressive symptoms after stroke, in light of their few side effects and lower cost ( Kang et al, 2021 ; Hu et al, 2023 ). However, despite the thriving evidence proving the remarkable therapeutic efficacy of EA for PID in clinical practice and randomized controlled trials, there are considerably fewer basic experiments regarding EA’s effects at the cellular level, particularly on neural cell types besides neurons, and this, to some extent, may limit our understanding of the mechanism of EA.…”

Electroacupuncture Ameliorates Depression-Like Behaviors in Post-Stroke Rats via Activating AMPK-Mediated Mitochondrial Function

“…15,16 In addition, some animal studies have found that EA treatment ameliorated depression-like behaviors by modulating the tPA/BDNF/TrkB signaling pathway in the prefrontal cortex. 17 However, till now, it is unknown whether AMPK-mediated mitochondrial function participates in the protective effects of EA treatment on PSD.…”

“…The expression of mitochondrial function-related proteins was found to be decreased in PSD rats, whereas EA treatment reversed these changes. 17 Based on this, we investigated the involvement of AMPK-mediated mitochondrial activity in the antidepressant effects of EA for the first time. Our results suggest that EA increased the endogenous p-AMPK expression and alleviated PSD-induced mitochondrial dysfunction, whereas blocking AMPK expression partially blocked the therapeutic effect of EA.…”