Department of Traditional Chinese Medicine, Xiangan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, PR China; Second Clinical College, Shanxi University of Traditional Chinese Medicine, Taiyuan, Shanxi, PR China.
The Fifth Hospital of Xiamen, Xiamen, Fujian, PR China.
Brain Res Bull. 2024 Nov;218:111108. doi: 10.1016/j.brainresbull.2024.111108. Epub 2024 Oct 22.
Our previous research has demonstrated that electroacupuncture (EA) has the potential to mitigate depression-like symptoms resulting from chronic stress. However, further investigation is required to fully understand the underlying mechanisms. The regulatory role of γ-aminobutyric acid type B (GABA) in synaptic plasticity and the involvement of NF-κB/NLRP3-mediated inflammation in the lateral habenula nucleus (LHb) are key factors in the development of depression. This study sought to investigate the potential of EA in mitigating depression-like symptoms induced by chronic stress through mechanisms such as enhancing GABA levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation.
Sprague-Dawley rats were exposed to chronic unpredictable mild stress (CUMS) in order to create a model of depression. Subsequently, the weight and behavioral assessments of all rats were monitored, and samples of the lateral habenula and serum were collected. The protein expression levels were analyzed using western blotting. The 5-hydroxytryptophan (5-HT), Dopamine (DA), and Norepinephrine (NE) in the LHb and serum were measured using ELISA. The alterations in GABA and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining.
EA upregulated the expression of GABA in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABA attenuated the antidepressant effects of EA in CUMS-exposed rats. Furthermore, EA enhanced synaptic plasticity in the LHb of CUMS-exposed rats and mitigated NF-κB/NLRP3-mediated inflammatory responses, with these effects potentially being reversed by GABA inhibition.
Through the promotion of GABA levels, regulation of synaptic plasticity within the LHb, and inhibition of NF-κB/NLRP3-mediated neuroinflammation in the same region, electroacupuncture at Shangxing and Fengfu acupoints demonstrates efficacy in mitigating depression-like behaviors induced by CUMS.
我们之前的研究表明，电针（EA）有可能缓解慢性应激引起的抑郁样症状。然而，需要进一步的研究来充分了解其潜在机制。γ-氨基丁酸 B 型（GABA）在突触可塑性中的调节作用和 NF-κB/NLRP3 介导的炎症在外侧缰核（LHb）中的参与是抑郁症发展的关键因素。本研究旨在通过提高 GABA 水平、调节 LHb 中的突触可塑性以及抑制 NF-κB/NLRP3 介导的炎症等机制，研究 EA 缓解慢性应激诱导的抑郁样症状的潜力。
将 Sprague-Dawley 大鼠暴露于慢性不可预测轻度应激（CUMS）中，以建立抑郁模型。随后，监测所有大鼠的体重和行为评估，并采集外侧缰核和血清样本。使用 Western 印迹分析蛋白表达水平。使用 ELISA 测量 LHb 和血清中的 5-羟色氨酸（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）。通过免疫荧光观察 LHb 中 GABA 和 NF-κB 的变化。通过尼氏染色评估 LHb 中的神经元损伤。
EA 上调了 CUMS 大鼠 LHb 中 GABA 的表达。随后的行为评估表明，阻断 GABA 会减弱 CUMS 暴露大鼠中 EA 的抗抑郁作用。此外，EA 增强了 CUMS 暴露大鼠 LHb 中的突触可塑性，并减轻了 NF-κB/NLRP3 介导的炎症反应，这些作用可能被 GABA 抑制所逆转。
通过促进 GABA 水平、调节 LHb 中的突触可塑性以及抑制同一区域的 NF-κB/NLRP3 介导的神经炎症，上行和凤府穴位电针对 CUMS 诱导的抑郁样行为具有疗效。
