Effect of “Tongdu Yupi Tiaoshen” electroacupuncture on behavioral performance and hippocampal structure and function in chronic fatigue syndrome rats

doi:10.19852/j.cnki.jtcm.2026.03.006

Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (3): 605-616.DOI: 10.19852/j.cnki.jtcm.2026.03.006

• Original Articles • Previous Articles Next Articles

Effect of “Tongdu Yupi Tiaoshen” electroacupuncture on behavioral performance and hippocampal structure and function in chronic fatigue syndrome rats

QU Yuanyuan¹^,², FENG Chuwen¹^,², SUN Weibo³, SHAO Yuying¹, LU Jing⁴, GUO Shuhao⁴, LI Binbin¹, YANG Tiansong¹^,²()

¹ Rehabilitation Department Ⅱ, the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin 150040, China
² Traditional Chinese Medicine Informatics Key Laboratory of Heilongjiang Province, Harbin 150040, China
³ Department of Breast Surgery, Harbin Medical University Affiliated Cancer Hospital, Harbin 150076, China
⁴ Graduate School of Heilongjiang University of Chinese Medicine, Harbin 150040, China

Received:2025-11-24 Accepted:2026-03-28 Online:2026-06-15 Published:2026-06-08
Contact: Prof. YANG Tiansong, Department of Rehabilitation, the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, and Traditional Chinese Medicine Informatics Key Laboratory of Heilongjiang Province, Harbin 150040, China. yangtiansong2006@163.com
Supported by:
National Natural Science Foundation of China (General Program): Mechanism of Electroacupuncture Regulating Mouse Double Minute 2 Ubiquitination of Postsynaptic Density protein-95 to Remodel Hippocampal Synaptic Structure and Improve Cognitive Dysfunction in Chronic Fatigue Syndrome(82074539);National Natural Science Foundation of China (Young Scientists Program): Role and Mechanism of Nuclear Factor Kappa B in Electroacupuncture Against Chronic Fatigue Syndrome Based on the Transforming Growth Factor-beta/Smad Signaling Pathway(81704170);Natural Science Foundation of Heilongjiang Province (General Program): Mechanism of Electroacupuncture Regulating Mitochondrial Dynamics to Promote Synaptic Remodeling in Chronic Fatigue Syndrome Rats with Cognitive Impairment(LH2024H050);Heilongjiang Province Postdoctoral Research Funding Program: Mechanism of Electroacupuncture Regulating p-T19 Postsynaptic Density protein-95 and Modulating Mitophagy in Synaptic Reconstruction to Improve Cognitive Impairment in Chronic Fatigue Syndrome Rats(LBH-Z24291);National Natural Science Foundation Cultivation Support Program (Young Scientists) of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine: Mechanism of Electroacupuncture Intervention in the Butyrate Gut-brain Axis Affecting p-T19 Postsynaptic Density Protein-95 to Promote Autophagy and Improve Cognitive Impairment in Chronic Fatigue Syndrome Rats(PYQN202501002);National Natural Science Foundation of China (Young Scientists Program): Mechanism of Moxibustion Activating Calcium-calmodulin-dependent Protein Kinase II Phosphorylation-mediated Long-term Potentiation to Regulate Synaptic Plasticity in Treating Chronic Fatigue Syndrome Cognitive Impairment(82305394);Ministry of Education “Chunhui Program” Collaborative Research Project: Mechanism of the “Tongdu Yupi Tiaoshen” Acupuncture Technique in Improving Hippocampal Synaptic Plasticity in Chronic Fatigue Syndrome Cognitive Dysfunction(HZKY20220308-202201357);Heilongjiang Provincial Traditional Chinese Medicine Research Project: Mechanism of Electroacupuncture in Regulating Hippocampal Synaptic Plasticity in Chronic Fatigue Syndrome Rats with Cognitive Dysfunction(ZHY2022-136);China Association of Chinese Medicine: Chinese Medicine Young Talent Support Project(CACM-2023-QNRC2-A04);Heilongjiang Provincial Association of Chinese Medicine Young Talent Support Project (2022-2024): Mechanism of the “Tongdu Yupi Tiaoshen” Acupuncture Technique in Improving Hippocampal Synaptic Plasticity in Chronic Fatigue Syndrome Cognitive Dysfunction(2022-QNRC1-05);Heilongjiang Provincial Key Research and Development Program Project (Directed Commission): Development of a Central-peripheral closed-loop Regulation Rehabilitation Robot for Post-stroke Cognitive Impairment Based on Traditional Chinese Medicine Acupuncture Theory(2024ZXDXC50)

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Abstract

Abstract:

OBJECTIVE: To investigate the effects of electroacupuncture intervention on behavioral performance, hippocampal structure, and function in chronic fatigue syndrome (CFS) rats and to explore the underlying mechanisms.

METHODS: Specific pathogen free-grade male Sprague-Dawley rats were randomly allocated into a control group (Con group, n =12) and a modeling group. The latter underwent a 21-d CFS induction viaan improved chronic multi-factor compound stress stimulation protocol. Successfully modeled CFS rats were then randomly assigned to a model group (Mod group, n =12) and an electroacupuncture group (EA group, n =12). During the 14-d treatment period, both the Mod and EA groups continued to receive chronic stress stimuli. Rats in the EA group received electroacupuncture at Shenting (GV24) through to Baihui (GV20), with additional stimulation on Dazhui (GV14). Each session lasted 15 min, administered twice daily with a 6-h interval between morning and afternoon treatments. After modeling and treatment, the general semi-quantitative score (GSQS) was used to evaluate the rats’ general health, while the Morris water maze test (MWMT), open field test (OFT), and exhaustive treadmill test (ETT) were applied to assess their learning/memory, emotional state, and fatigue levels, respectively (n =12 per group). After the treatment phase, cerebral glucose metabolism was assessed by ¹;⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging (n =3 per group), while hippocampal cornu ammonis 1 (CA1) morphology was examined using hematoxylin-eosin (HE) and Nissl staining (n =3 per group).

RESULTS: Behavioral assessments demonstrated that electroacupuncture intervention significantly improved rat performance as measured by GSQS, MWMT, OFT, and Exhaustive Treadmill Test. Both HE and Nissl staining results confirmed that, compared with the blank control group, the model group exhibited abnormal cellular morphology, disorganized arrangement, and reduced Nissl bodies in the hippocampal CA1 region. These pathological alterations were ameliorated in the electroacupuncture group relative to the model group. 18F-FDG PET/CT imaging revealed that following treatment, the mean and maximum standardized uptake values (SUV) in the anterior-dorsal and posterior hippocampus were significantly decreased in the Mod group compared to the Con group. In contrast, electroacupuncture treatment significantly increased both SUV-mean and SUV-max in these hippocampal subregions in the EA group relative to the Mod group (all P <0.05).

CONCLUSION: Electroacupuncture intervention alleviated cognitive impairment, hippocampal pathological structural changes, and glucose metabolism dysfunction in a rat model of chronic fatigue syndrome induced by an improved chronic multi-factor compound stress stimulation method.

Key words: electroacupuncture, chronic fatigue syndrome, cognitive dysfunction, hippocampal structures, hippocampal functions

QU Yuanyuan, FENG Chuwen, SUN Weibo, SHAO Yuying, LU Jing, GUO Shuhao, LI Binbin, YANG Tiansong. Effect of “Tongdu Yupi Tiaoshen” electroacupuncture on behavioral performance and hippocampal structure and function in chronic fatigue syndrome rats[J]. Journal of Traditional Chinese Medicine, 2026, 46(3): 605-616.

Figures/Tables 6

Table 1 Comparison of GSQS in treatment phase ($\bar{x}$ ± s)

Group	n	Day 1	Day 8	Day 15
Con	12	0.8±0.4	0.8±0.4	1.1±0.7
Mod	12	5.7±0.8^a	6.2±0.7^a	7.1±0.7^a
EA	12	5.9±0.8	4. 7±0.5^b	3.0±0.6^b

Table 2 Post-treatment MWMT results ($\bar{x}$ ± s)

Group	n	Escape latency				Target platform crossings
Group	n	Day 1	Day 2	Day 3	Day 4	Target platform crossings
Con	12	29.7±2.8	19.9±4.8	12.8±4.6	11.3±5.1	3.8±0.9
Mod	12	44.0±2.5^a	30.5±4.4^a	28.7±5.8^a	27.1±6.0^a	1.8±1.0^a
EA	12	30.3±5.6^b	12.9±5.5^b	14.7±5.5^b	13.4±7.4^b	3.5±0.5^b

Table 3 Post-treatment results of OFT and exhaustive treadmill running time ($\bar{x}$ ± s)

Group	n	OFT		Exhaustive treadmill running time
Group	n	Grid crossings	Central area entries	Exhaustive treadmill running time
Con	12	30.2±15.8	3.7±1.2	101.6±8.6
Mod	12	66.2±25.3^a	9.4±2.5^a	73.4±7.9^a
EA	12	40.6±24.2^b	5.9±1.2^b	92.1±8.5^b

Figure 1 Structural changes in the hippocampal CA1 region (n = 3) A: hematoxylin-eosin staining results of hippocampal CA1 region; B: Nissl staining results of hippocampal CA1 region; Scale bar = 50 μm. A1, B1: Con group; A2, B2: Mod group; A3, B3: EA group. Con: normal control group, with routine feeding and sham restraint; Mod: chronic fatigue syndrome model group, with 14-d continuous stress stimulation; EA: electroacupuncture treatment group, with 14-d “Tongdu Yupi Tiaoshen” electroacupuncture intervention. CA1: cornu ammonis 1. The red box highlights sparse neuronal arrangement in the hippocampal CA1 region; arrows indicate Nissl bodies.

Table 4 Hippocampal 18F-FDG PET/CT imaging results (%ID/g, $\bar{x}$ ± s)

Group	n	SUV	Anterior-dorsal hippocampus (L)	Anterior-dorsal hippocampus (R)	Posterior hippocampus (L)	Posterior hippocampus (R)
Con	3	Mean	0.429±0.092	0.423±0.082	0.452±0.060	0.436±0.068
	3	Max	0.526±0.080	0.508±0.084	0.538±0.077	0.513±0.064
Mod	3	Mean	0.239±0.056^a	0.242±0.072^a	0.252±0.075^a	0.256±0.080^a
	3	Max	0.326±0.064^a	0.307±0.080^a	0.310±0.079^a	0.299±0.083^a
EA	3	Mean	0.381±0.015^b	0.372±0.009^b	0.400±0.011^b	0.407±0.012^b
	3	Max	0.513±0.013^b	0.470±0.012^b	0.486±0.018^b	0.481±0.018^b

Figure 2 Hippocampal 18F-FDG PET/CT imaging results (n = 3) Three-view diagram of brain sections. A: Con group; B: Mod group; C: EA group; D: the color bar on the right indicates high, medium, and low glucose metabolism levels from top to bottom. Con: normal control group, with routine feeding and sham restraint; Mod: chronic fatigue syndrome model group, with 14-d continuous stress stimulation; EA: electroacupuncture treatment group, with 14-d “Tongdu Yupi Tiaoshen” electroacupuncture intervention. 18F-FDG PET/CT: 1;⁸F‑fluorodeoxyglucose positron emission tomography/computed tomography.

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Effect of “Tongdu Yupi Tiaoshen” electroacupuncture on behavioral performance and hippocampal structure and function in chronic fatigue syndrome rats

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