Electroacupuncture Alleviates Comorbid Depression‐Like Behaviors and Dyspepsia‐Like Symptoms in Rats Accompanied by Alterations in Hippocampal Neuroinflammation and Gut Microbiota
- 1Liaoning University of Traditional Chinese Medicine
Abstract
Background Depression and dyspepsia are highly comorbid in clinical practice, and their occurrence and progression are closely associated with dysfunction of the brain–gut axis. Electroacupuncture (EA) can improve depression and gastrointestinal dysfunction at the same time. However, whether its therapeutic effects are mediated through regulation of the brain–gut axis remains unclear. Methods We established a rat model of comorbid depression‐like and dyspepsia‐like symptoms using SD rats. Behavioral tests were used to evaluate anxiety‐ and depression‐like states in rats. Gastric emptying rate, small intestinal propulsion rate, and gastrointestinal hormones were measured to assess gastrointestinal motility. Histomorphological changes in the hippocampus, stomach, and duodenum were observed by hematoxylin–eosin (HE) staining and Nissl staining. Immunofluorescence (IF), Western blotting, quantitative real‐time polymerase chain reaction (RT‐qPCR), and biochemical assays were used to determine the activation status of hippocampal microglia and mitochondrial reactive oxygen species (mtROS)/NOD‐like receptor family pyrin domain containing 3 (mtROS/NLRP3) pathway‐related indicators. Enzyme‐linked immunosorbent assay was used to determine central and peripheral levels of 5‐hydroxytryptamine (5‐HT) and inflammatory factors. Gut microbiota diversity and composition were analyzed by 16S rRNA sequencing. The expression of duodenal mucosal barrier‐related proteins was detected by immunofluorescence, and the ultrastructure of the duodenum was observed by transmission electron microscopy. Results EA significantly alleviated anxiety‐ and depression‐like behaviors and improved gastrointestinal motility in model rats. EA ameliorated hippocampal neuronal injury, increased Nissl body number, reduced mtROS and malondialdehyde levels, enhanced mitochondrial membrane potential and superoxide dismutase activity, and suppressed microglial activation and NLRP3 inflammasome signaling. In addition, EA increased central and peripheral 5‐HT levels while decreasing Interleukin‐6 (IL‐6) and tumor necrosis factor‐α expression. EA also modulated gut microbiota composition by reducing opportunistic pathogens and enriching beneficial bacteria. Moreover, EA improved duodenal ultrastructure and upregulated the tight junction proteins ZO‐1 and Occludin. Conclusion EA can improve depression‐like behaviors and dyspepsia‐like symptoms in comorbid rats. These behavioral and gastrointestinal improvements were accompanied by reduced hippocampal oxidative stress and neuroinflammation, altered gut microbiota composition, and improved duodenal mucosal barrier. These findings suggest that the therapeutic mechanism of EA may involve regulation of the brain–gut axis, although the specific causal relationships among its individual components remain to be elucidated.
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BibTeX
@article{wang2026electroacupuncture,
title = {{Electroacupuncture Alleviates Comorbid Depression‐Like Behaviors and Dyspepsia‐Like Symptoms in Rats Accompanied by Alterations in Hippocampal Neuroinflammation and Gut Microbiota}},
author = {Tianlang Wang and Yifan Feng and Xihan Wang and Yanan Xue and Jianbo Wang and Yi Qu and Tieming Ma and Jidong Liu},
journal = {Brain and behavior},
year = {2026},
month = oct,
doi = {10.1002/brb3.71854},
url = {https://europepmc.org/article/PMC/PMC13691533},
note = {CC BY},
}
RIS
TY - JOUR
TI - Electroacupuncture Alleviates Comorbid Depression‐Like Behaviors and Dyspepsia‐Like Symptoms in Rats Accompanied by Alterations in Hippocampal Neuroinflammation and Gut Microbiota
AU - Tianlang Wang
AU - Yifan Feng
AU - Xihan Wang
AU - Yanan Xue
AU - Jianbo Wang
AU - Yi Qu
AU - Tieming Ma
AU - Jidong Liu
PY - 2026
DA - 2026/10/01
JO - Brain and behavior
DO - 10.1002/brb3.71854
UR - https://europepmc.org/article/PMC/PMC13691533
AB - Background Depression and dyspepsia are highly comorbid in clinical practice, and their occurrence and progression are closely associated with dysfunction of the brain–gut axis. Electroacupuncture (EA) can improve depression and gastrointestinal dysfunction at the same time. However, whether its therapeutic effects are mediated through regulation of the brain–gut axis remains unclear. Methods We established a rat model of comorbid depression‐like and dyspepsia‐like symptoms using SD rats. Behavioral tests were used to evaluate anxiety‐ and depression‐like states in rats. Gastric emptying rate, small intestinal propulsion rate, and gastrointestinal hormones were measured to assess gastrointestinal motility. Histomorphological changes in the hippocampus, stomach, and duodenum were observed by hematoxylin–eosin (HE) staining and Nissl staining. Immunofluorescence (IF), Western blotting, quantitative real‐time polymerase chain reaction (RT‐qPCR), and biochemical assays were used to determine the activation status of hippocampal microglia and mitochondrial reactive oxygen species (mtROS)/NOD‐like receptor family pyrin domain containing 3 (mtROS/NLRP3) pathway‐related indicators. Enzyme‐linked immunosorbent assay was used to determine central and peripheral levels of 5‐hydroxytryptamine (5‐HT) and inflammatory factors. Gut microbiota diversity and composition were analyzed by 16S rRNA sequencing. The expression of duodenal mucosal barrier‐related proteins was detected by immunofluorescence, and the ultrastructure of the duodenum was observed by transmission electron microscopy. Results EA significantly alleviated anxiety‐ and depression‐like behaviors and improved gastrointestinal motility in model rats. EA ameliorated hippocampal neuronal injury, increased Nissl body number, reduced mtROS and malondialdehyde levels, enhanced mitochondrial membrane potential and superoxide dismutase activity, and suppressed microglial activation and NLRP3 inflammasome signaling. In addition, EA increased central and peripheral 5‐HT levels while decreasing Interleukin‐6 (IL‐6) and tumor necrosis factor‐α expression. EA also modulated gut microbiota composition by reducing opportunistic pathogens and enriching beneficial bacteria. Moreover, EA improved duodenal ultrastructure and upregulated the tight junction proteins ZO‐1 and Occludin. Conclusion EA can improve depression‐like behaviors and dyspepsia‐like symptoms in comorbid rats. These behavioral and gastrointestinal improvements were accompanied by reduced hippocampal oxidative stress and neuroinflammation, altered gut microbiota composition, and improved duodenal mucosal barrier. These findings suggest that the therapeutic mechanism of EA may involve regulation of the brain–gut axis, although the specific causal relationships among its individual components remain to be elucidated.
SN - 2162-3279
ER -