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电针对慢性不可预测轻度应激大鼠的转录组分析。

Transcriptome analysis of rats with chronic unpredictable mild stress treated with electroacupuncture.

机构信息

Acupuncture Research Institute, Shandong University of Traditional Chinese Medicine, Jinan, China.

School of Acupuncture and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Brain Behav. 2024 Sep;14(9):e70045. doi: 10.1002/brb3.70045.


DOI:10.1002/brb3.70045
PMID:39295096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11410874/
Abstract

BACKGROUND: Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Electroacupuncture (EA), a nonpharmacologic therapy, holds great promise for alleviating depressive symptoms. In this study, RNA sequencing (RNA-Seq) was used to identify genome-wide alterations in the hippocampus of rats after chronic unpredictable mild stress (CUMS) and EA treatments to further elucidate the mechanism by which EA ameliorates depression to provide a basis for the clinical application of EA in stress-related diseases. METHODS: The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to investigate the ability of EA at Baihui (GV20) and Taichong acupoints (LR3) to improve depression-like behavior in rats subjected to CUMS. Subsequently, RNA-Seq analysis revealed transcriptomic profiles of the hippocampus of rats subjected to CUMS in which EA ameliorated depressive behavior. Finally, the expression profiles of major differentially expressed genes were tested by real-time quantitative polymerase chain reaction (qRT-PCR) to determine the accuracy of the RNA-Seq results. RESULTS: Rats subjected to CUMS exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT (p < .001), decreased time in the central area of the OFT (p < .001), and increased immobility in the FST (p < .01). Importantly, rats subjected to CUMS and treated with EA showed increased sucrose consumption (p < .001), increased time spent in the central area of the OFT (p < .001) and decreased immobility in the FST (p < .01). Sixty-three genes that were differentially expressed following CUMS were altered by EA; most of these were associated with immune pathways. Compared with those in the control group, the expression levels of Colla2 (p < .001), Col3a1 (p < .001), Psmb9 (p < .01), and Tap1 (p < .01) in the hippocampus of rats subjected to CUMS were lower. The changes in the expression of these genes were reversed by EA treatment. CONCLUSION: EA at GV20 and LR3 attenuated CUMS-induced depression-like behaviors by regulating the expression of specific genes such as Colla2, Col3a1, Psmb9, and Tap1.

摘要

背景:抑郁症仍是最常见的精神疾病之一,许多患者对现有治疗方法的反应不佳。电针(EA)作为一种非药物治疗方法,在缓解抑郁症状方面具有很大的潜力。在这项研究中,我们使用 RNA 测序(RNA-Seq)来鉴定慢性不可预测轻度应激(CUMS)和 EA 治疗后大鼠海马体的全基因组改变,以进一步阐明 EA 改善抑郁的机制,为 EA 在应激相关疾病中的临床应用提供依据。 方法:采用蔗糖偏好试验(SPT)、旷场试验(OFT)和强迫游泳试验(FST),探讨电针百会(GV20)和太冲(LR3)穴对 CUMS 大鼠抑郁样行为的改善作用。随后,RNA-Seq 分析揭示了 EA 改善抑郁行为的 CUMS 大鼠海马体的转录组谱。最后,通过实时定量聚合酶链反应(qRT-PCR)检测主要差异表达基因的表达谱,以确定 RNA-Seq 结果的准确性。 结果:CUMS 大鼠表现出抑郁样行为,如 SPT 中蔗糖消耗减少(p<0.001)、OFT 中央区时间减少(p<0.001)和 FST 中不动时间增加(p<0.01)。重要的是,CUMS 大鼠经 EA 治疗后,蔗糖消耗增加(p<0.001),OFT 中央区时间增加(p<0.001),FST 不动时间减少(p<0.01)。63 个基因在 CUMS 后发生差异表达,经 EA 后发生改变;其中大多数与免疫途径有关。与对照组相比,CUMS 大鼠海马体中 Colla2(p<0.001)、Col3a1(p<0.001)、Psmb9(p<0.01)和 Tap1(p<0.01)的表达水平较低。EA 治疗可逆转这些基因表达的变化。 结论:GV20 和 LR3 的 EA 通过调节 Colla2、Col3a1、Psmb9 和 Tap1 等特定基因的表达,减轻 CUMS 诱导的抑郁样行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/6f3a0e746790/BRB3-14-e70045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/22671d6db1d8/BRB3-14-e70045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/2fb601c73371/BRB3-14-e70045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/db06bdacd57a/BRB3-14-e70045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/252fa0a32a99/BRB3-14-e70045-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/ebe1d57f5d46/BRB3-14-e70045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/1794f4356569/BRB3-14-e70045-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/6f3a0e746790/BRB3-14-e70045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/22671d6db1d8/BRB3-14-e70045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/2fb601c73371/BRB3-14-e70045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/db06bdacd57a/BRB3-14-e70045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/252fa0a32a99/BRB3-14-e70045-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/ebe1d57f5d46/BRB3-14-e70045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/1794f4356569/BRB3-14-e70045-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d9/11410874/6f3a0e746790/BRB3-14-e70045-g001.jpg

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本文引用的文献

[1]
Hypothalamic Gene Expression in a Rat Model of Chronic Unpredictable Mild Stress Treated with Electroacupuncture.

Neurochem Res. 2024-5

[2]
Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis.

Brain Res. 2024-3-1

[3]
Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis.

J Neuroinflammation. 2023-11-27

[4]
Acupuncture Ameliorates Depression-Like Behaviors Through Modulating the Neuroinflammation Mediated by TLR4 Signaling Pathway in Rats Exposed to Chronic Restraint Stress.

Mol Neurobiol. 2024-5

[5]
Inhibition of ferroptosis alleviates chronic unpredictable mild stress-induced depression in mice via tsRNA-3029b.

Brain Res Bull. 2023-11

[6]
Immune gene co-expression signatures implicated in occurence and persistence of cognitive dysfunction in depression.

Prog Neuropsychopharmacol Biol Psychiatry. 2023-12-20

[7]
Correlation between immune-related genes and depression-like features in an animal model and in humans.

Brain Behav Immun. 2023-10

[8]
Anti-neuroinflammation effects of transcutaneous auricular vagus nerve stimulation against depression-like behaviors via hypothalamic α7nAchR/JAK2/STAT3/NF-κB pathway in rats exposed to chronic unpredictable mild stress.

CNS Neurosci Ther. 2023-9

[9]
Genes of the Ubiquitin Proteasome System Qualify as Differential Markers in Malignant Glioma of Astrocytic and Oligodendroglial Origin.

Cell Mol Neurobiol. 2023-5

[10]
Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression.

J Neuroinflammation. 2022-6-6

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