---
title: "Electroacupuncture at LI4/LR3 reduces CRS-induced depressive-like behavior via PVN CRH neuron modu"
id: "pubmed-42908448"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42908448"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42908448/"
doi: "10.13702/j.1000-0607.20260563"
published_at: "2026-10-25T00:00:00.000Z"
evidence_level: "English Abstract"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Electroacupuncture at LI4/LR3 reduces CRS-induced depressive-like behavior via PVN CRH neuron modu
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42908448
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42908448/)
- **DOI:** [10.13702/j.1000-0607.20260563](https://doi.org/10.13702%2Fj.1000-0607.20260563)
- **Published At:** 2026-10-25T00:00:00.000Z
- **Evidence Rating:** English Abstract
## Executive GIST (TL;DR)
- Investigators used male C57BL/6J and CRH-Cre mice to model chronic restraint stress (CRS) and test bilateral electroacupuncture (EA) at **LI4** and **LR3**. EA parameters reported were 2 Hz, 0.5 mA, 30 minutes daily for seven days. - The behavioral battery included forced swim test, tail suspension test, and open-field test; the model cohort showed increased immobility and peripheral-zone locomotion compared with blank controls. - Serum endocrine measures (ELISA) included **CRH**, ACTH and corticosterone (CORT); CRS elevated all three markers versus blank controls according to the authors. - EA shortened immobility times in forced swim and tail suspension tests and reduced peripheral-zone distance in the open-field test relative to the CRS model group. - EA reduced serum ACTH and CORT significantly; serum **CRH** trended lower but did not reach statistical significance in the reported results. - PVN neuronal activation was assessed by c-Fos immunofluorescence; CRS increased PVN c-Fos counts and the percentage of c-Fos among mCherry-labeled PVN **CRH** neurons; EA reduced both measures. - Fiber photometry recorded event-related PVN **CRH** neuron calcium activity (ΔF/F). The area under the curve and peak ΔF/F in the 0–5 s window were lower during and after EA versus pre-EA baselines. - Chemogenetic activation (CNO) of PVN **CRH** neurons under subthreshold stress prolonged immobility and reduced peripheral locomotion; subsequent EA reversed those behavioral effects according to the authors. - The study team concluded EA at LI4/LR3 ameliorates CRS-induced depressive-like behaviors through down-regulation of **HPA axis** hormone responses, reduced PVN activation, and modulation of PVN **CRH** neuron calcium signals. - The source did not provide detailed method elements such as exact group sizes per experiment, randomization procedures, blinding, or longer-term follow-up beyond the reported 7-day EA regimen.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China. * 2 The Ninth Clinical Medical College, Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province. * 3 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120. * 4 Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China. xueaiguo@126.com. * PMID: **42908448** * DOI: [ 10.13702/j.1000-0607.20260563 ](https://doi.org/10.13702/j.1000-0607.20260563) Item in Clipboard # [Electroacupuncture ameliorates chronic restraint stress-induced depressive-like behavior by modulating paraventricular nucleus corticotropin-releasing hormone neuron activity in mice] [Article in Chinese] Derong Lin et al. Zhen Ci Yan Jiu. 2026. Show details Display options Display options Format Abstract PubMed PMID Zhen Ci Yan Jiu Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Zhen+Ci+Yan+Jiu%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Zhen+Ci+Yan+Jiu%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42908448/) . 2026 Oct 25;51(10):1319-1328. doi: 10.13702/j.1000-0607.20260563. ### Authors [Derong Lin](https://pubmed.ncbi.nlm.nih.gov/?term=Lin+D&cauthor_id=42908448)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-1 "Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-2 "The Ninth Clinical Medical College, Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province."), [Sheng Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+S&cauthor_id=42908448)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-3 "The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120."), [Jianpeng Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+J&cauthor_id=42908448)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-3 "The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120."), [Shuxiong Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+S&cauthor_id=42908448)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-1 "Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China."), [Jianhua Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+J&cauthor_id=42908448)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-3 "The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120."), [Aiguo Xue](https://pubmed.ncbi.nlm.nih.gov/?term=Xue+A&cauthor_id=42908448)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42908448/#short-view-affiliation-4 "Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China. xueaiguo@126.com.") ### Affiliations * 1 Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China. * 2 The Ninth Clinical Medical College, Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province. * 3 The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120. * 4 Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, Guangdong Province, China. xueaiguo@126.com. * PMID: **42908448** * DOI: [ 10.13702/j.1000-0607.20260563 ](https://doi.org/10.13702/j.1000-0607.20260563) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract in [ English, ](https://pubmed.ncbi.nlm.nih.gov/42908448/#eng-abstract) [ Chinese ](https://pubmed.ncbi.nlm.nih.gov/42908448/#zho-abstract) **Objectives:** To investigate the effect of electroacupuncture (EA) at "Hegu" (LI4) and "Taichong" (LR3) on depressive-like behaviors and corticotropin-releasing hormone (CRH) neuron-related activity in paraventricular nucleus (PVN) in mice exposed to chronic restraint stress (CRS), so as to explore its possible mechanism. **Methods:** Male C57BL/6J mice and CRH-Cre mice were used in the separate experimental cohorts of this study. A CRS-induced depressive-like behavior model was established and treated with bilateral EA at LI4 and LR3 (2 Hz, 0.5 mA, 30 min in duration of stimulation, once daily for 7 d). Behavioral changes were evaluated using forced swimming, tail suspension and open-field tests. Serum CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were measured using ELISA. The PVN neuronal activation and the proportion of c-Fos-positive cells among mCherry-labeled PVN CRH neurons were evaluated using immunofluorescence staining and c-Fos/mCherry co-labeling. Event-related PVN CRH neuron calcium activity was recorded by using fiber photometry. Chemogenetic activation with clozapine-N-oxide (CNO) was further used to observe the behavioral changes under subthreshold stress and EA intervention effect. **Results:** Compared with the blank group, the model group showed a significant increase in the immobility time in the forced swimming and tail suspension tests (_P_ <0.01, _P_ <0.001), distance traveled in the peripheral zone in the open-field test (_P_ <0.001), contents of serum CRH, ACTH and CORT (_P_ <0.000 1, _P_ <0.001), number of c-Fos positive cell in the PVN (_P_ <0.05), and the percentage of c-Fos/mCherry double-positive cells among the mCherry-positive cells (_P_ <0.05). Compared with the model group, EA shortened the immobility time in the forced swimming and tail suspension tests (_P_ <0.05), decreased the distance traveled in the peripheral zone of the open-field test (_P_ <0.001), reduced the contents of serum ACTH and CORT (_P_ <0.05, _P_ <0.000 1), and decreased the number of PVN c-Fos-positive cell and the percentage of c-Fos/mCherry double-positive cells among the mCherry-positive cells (_P_ <0.05), while serum CRH presented a lowering trend without statistically significant difference. The ΔF/F area under the curve and peak ΔF/F within the 0-5 s time window were considerably lower during and after EA than EA pre-treatment (_P_ <0.001, _P_ <0.05, _P_ <0.000 1). Under the subthreshold stress, chemogenetic activation of PVN CRH neurons prolonged the immobility time in the forced swimming and tail suspension tests (_P_ <0.000 1, _P_ <0.001) and reduced the distance traveled in the peripheral zone in the open-field test (_P_ <0.05, _P_ <0.001);after EA, these behavioral changes were reversed (_P_ <0.001, _P_ <0.000 1, _P_ <0.05). **Conclusions:** EA at LI4 and LR3 can ameliorate CRS-induced depressive-like behaviors by down-regulating hypothalamic-pituitary-adrenal axis-related hormone responses, reducing PVN neuronal activation, decreasing the proportion of c-Fos-positive cells among the mCherry-labeled PVN CRH neurons, and modulating event-related PVN CRH neuron calcium activity. **目的** : 观察电针“合谷”“太冲”对慢性束缚应激（CRS）小鼠抑郁样行为及下丘脑室旁核（PVN）促肾上腺皮质激素释放激素（CRH）神经元相关活动的影响，并探讨其可能机制。**方法** : 雄性C57BL/6J小鼠和CRH-Cre小鼠按实验目的分队列检测。采用CRS建立抑郁样行为模型。电针组给予电针双侧“合谷”“太冲”干预。采用强迫游泳、悬尾和旷场实验评价行为学变化，ELISA法检测血清CRH、促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平，免疫荧光法及c-Fos/mCherry共标法检测PVN区神经元激活及mCherry标记的PVN CRH神经元中c-Fos阳性比例，以光纤钙成像记录PVN区CRH神经元事件相关钙活动;采用氯氮平-N-氧化物激活PVN区CRH神经元，观察阈下应激小鼠行为学变化及电针效应。**结果** : 与空白组比较，模型组强迫游泳和悬尾不动时间延长（ _P <_0.01， _P_ <0.001），旷场周围行程增加（ _P_ <0.001），血清CRH、ACTH和CORT水平升高（ _P_ <0.000 1， _P_ <0.001），PVN区c-Fos阳性细胞数及c-Fos/mCherry双阳性细胞占mCherry阳性细胞百分比上升（ _P_ <0.05）。与模型组比较，电针组强迫游泳和悬尾不动时间缩短（ _P <_0.05），旷场周围行程减少（ _P_ <0.001），血清ACTH和CORT水平下降（ _P_ <0.05， _P_ <0.000 1），PVN区c-Fos阳性细胞数及c-Fos/mCherry双阳性细胞占mCherry阳性细胞百分比下降（ _P_ <0.05），血清CRH水平呈降低趋势但差异无统计学意义。与针刺前比较，针刺期间和针刺后PVN区CRH神经元0~5 s时间窗内ΔF/F曲线下面积和峰值ΔF/F降低（ _P_ <0.001， _P_ <0.05， _P_ <0.000 1）。阈下应激条件下，化学遗传学激活PVN区CRH神经元可延长强迫游泳实验和悬尾实验的不动时间（ _P_ <0.000 1， _P_ <0.001），减少旷场实验的周围行程（ _P_ <0.05， _P_ <0.001），电针干预可减轻上述改变（ _P_ <0.001， _P_ <0.000 1， _P_ <0.05）。**结论** : 电针“合谷”“太冲”可改善CRS小鼠抑郁样行为，其作用可能与降低下丘脑-垂体-肾上腺轴相关激素反应、减弱PVN区神经元激活、降低PVN区CRH神经元中c-Fos阳性比例及调节PVN区CRH神经元事件相关钙活动有关。. **Keywords:** Chemogenetics; Chronic restraint stress; Corticotropin-releasing hormone; Depressive-like behavior; Electroacupuncture; Fiber photometry; Paraventricular nucleus. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement All authors declare that there is no conflict of interest. ## References 1. 1. Marx W, Penninx B W J H, Solmi M, et al. Major depressive disorder[J]. Nat Rev Dis Primers, 2023, 9:44. 2. 1. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019:a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet Psychiatry, 2022, 9(2):137-150. 3. 1. Marwaha S, Palmer E, Suppes T, et al. Novel and emerging treatments for major depression[J]. Lancet, 2023, 401(10371):141-153. 4. 1. Chen B L, Wang C C, Lee K H, et al. Efficacy and safety of acupuncture for depression:a systematic review and meta-analysis[J]. Res Nurs Health, 2023, 46(1):48-67. 5. 1. Tan Y W, Duan R Q, Wen C B. Efficacy of acupuncture for depression:a systematic review and meta-analysis[J]. Front Neurosci, 2024, 18:1347651. 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> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.