Lyu Qin, Shi Liu-Qing, Chen Hai-Yang, Lu Mei, Liang Xi-Cai, Ma Xian-De, Zhou Xin, Ren Lu
Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Department of Acupuncture and Moxibustion, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China.
Life Sci. 2024 Dec 15;359:123235. doi: 10.1016/j.lfs.2024.123235. Epub 2024 Nov 9.
Electroacupuncture (EA) is a form of Traditional Chinese Medicine (TCM) that combines acupuncture with microcurrents mimicking the body's bioelectricity to prevent and treat diseases. Previous studies have demonstrated its antidepressant-like effects in chronic unpredictable mild stress (CUMS)-induced ovariectomy (OVX) rats. Neural stem cell-derived exosomes (NSCs-Exo) are heterogeneous and targeted, effectively promoting nerve regeneration and repairing neuronal damage, while potentially conveying the effects of EA. However, the precise mechanism remains unclear. In this study, perimenopausal depressive disorder (PDD) rat model were established using a two-step protocol CUMS + OVX. Treatment with EA combined with NSCs-Exo (EA-Exo) significantly improved depression-like behaviors in PDD rats, as indicated by increased sucrose intake in the Sucrose Preference Test (SPT), reduced immobility in the Forced Swimming Test (FST), and prolonged activity in the Out-of-Field Test (OFT). EA-Exo treatment improved depression-like behaviors by increasing serum levels of 5-hydroxytryptamine (5-HT) and decreasing immobility in the FST. It also alleviated OVX-CUMS-induced disturbances in energy metabolism, inflammation, and oxidative stress responses by enhancing serum levels of 5-HT, dopamine (DA), ATP, superoxide dismutase (SOD), and interleukin-10 (IL-10), while reducing cyclic AMP (cAMP), interleukin-6 (IL-6), reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, EA-Exo treatment reversed structural and functional impairments in hippocampal synapses and mitochondria. This was evidenced by reductions in hippocampal synaptic plasticity proteins PSD95, SYN, and GAP43, as well as decreased expression of energy metabolism pathway proteins AMPK, NRF1, PGC1α, and TFAM. These findings suggest that EA-Exo ameliorates depressive behavior in OVX-CUMS rats by modulating synaptic plasticity and activating the AMPK/NRF1/PGC1α/TFAM signaling pathway.
电针是一种将针刺与模拟人体生物电的微电流相结合以预防和治疗疾病的中医疗法。先前的研究已证明其在慢性不可预测轻度应激（CUMS）诱导的去卵巢（OVX）大鼠中具有抗抑郁样作用。神经干细胞衍生的外泌体（NSCs-Exo）具有异质性且具有靶向性，能有效促进神经再生和修复神经元损伤，同时可能传递电针的作用。然而，确切机制仍不清楚。在本研究中，采用两步法CUMS + OVX建立围绝经期抑郁症（PDD）大鼠模型。电针联合NSCs-Exo（EA-Exo）治疗显著改善了PDD大鼠的抑郁样行为，如蔗糖偏好试验（SPT）中蔗糖摄入量增加、强迫游泳试验（FST）中不动时间减少以及旷场试验（OFT）中活动时间延长所示。EA-Exo治疗通过提高血清5-羟色胺（5-HT）水平并减少FST中的不动时间来改善抑郁样行为。它还通过提高血清5-HT、多巴胺（DA）、三磷酸腺苷（ATP）、超氧化物歧化酶（SOD）和白细胞介素-10（IL-10）水平，同时降低环磷酸腺苷（cAMP）、白细胞介素-6（IL-6）、活性氧（ROS）和丙二醛（MDA）水平，减轻了OVX-CUMS诱导的能量代谢、炎症和氧化应激反应紊乱。此外，EA-Exo治疗逆转了海马突触和线粒体的结构和功能损伤。这通过海马突触可塑性蛋白PSD95、SYN和GAP43的减少以及能量代谢途径蛋白AMPK、NRF1、PGC1α和TFAM表达的降低得以证明。这些发现表明，EA-Exo通过调节突触可塑性和激活AMPK/NRF1/PGC1α/TFAM信号通路改善OVX-CUMS大鼠的抑郁行为。
