GABAB modulate NF-κB/NLRP3 pathways in electroacupuncture prevention of depression in CUMS rats

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2024-10-22 DOI:10.1016/j.brainresbull.2024.111108

Jianguo Li , Dong Yao , Tiansheng Zhang , Tao Tong , Junliang Shen , Simin Yan , Jingyu Zeng , Muhammad Shahzad Aslam , Meng Li , Zhuoran You , Jingxuan Li , Zhongwen Li , Yizheng Li , Chongyao Hao , Xianjun Meng

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引用次数: 0

Abstract

Background

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_B) 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_B levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation.

Methods

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_B and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining.

Results

EA upregulated the expression of GABA_B in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABA_B 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_B inhibition.

Conclusion

Through the promotion of GABA_B 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.

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GABAB调节NF-κB/NLRP3通路在电针预防CUMS大鼠抑郁中的作用

背景：我们之前的研究表明，电针（EA）具有减轻慢性压力导致的抑郁症状的潜力。然而，要充分了解其潜在机制还需要进一步的研究。γ-氨基丁酸 B 型（GABAB）在突触可塑性中的调节作用以及 NF-κB/NLRP3 介导的外侧哈文氏核（LHb）炎症是抑郁症发病的关键因素。本研究试图探讨EA通过提高GABAB水平、调节LHb的突触可塑性和抑制NF-κB/NLRP3介导的炎症等机制减轻慢性应激诱发的抑郁症状的潜力：方法：将 Sprague-Dawley 大鼠暴露于慢性不可预测的轻度应激（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，并采集外侧脑膜和血清样本。蛋白质表达水平采用 Western 印迹法进行分析。用酶联免疫吸附法测定了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）。免疫荧光法观察了LHb中GABAB和NF-κB的变化。用Nissl染色法评估LHb中神经元的损伤情况：结果：EA上调了CUMS大鼠LHb中GABAB的表达。随后的行为评估表明，阻断GABAB会减弱EA对CUMS暴露大鼠的抗抑郁作用。此外，EA还增强了暴露于CUMS的大鼠LHb的突触可塑性，减轻了NF-κB/NLRP3介导的炎症反应，而抑制GABAB可能会逆转这些效应：结论：通过促进GABAB水平、调节LHb内的突触可塑性以及抑制NF-κB/NLRP3介导的神经炎症反应，电针上星穴和风府穴可有效缓解CUMS诱导的抑郁样行为。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.