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Published on: June 6, 2025
Acupuncture attenuates depression-like behavior by modulating the glu-mGluR3-BDNF signaling pathway in the prefrontal
Meng Li1, Zhuoran You2, Jingyu Zeng3
1Department of Traditional Chinese Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Shuanghe Vocational and Technical College, Shuanghe, Xinjiang, China; Shenzhen Research Institute of Xiamen University, Shenzhen, PR China.
Acupuncture effectively reduces depression-like behaviors in rats by modulating the glutamate-mGluR3-BDNF pathway in the prefrontal cortex. These findings highlight acupuncture
Area of Science:
- Neuroscience
- Integrative and Complementary Medicine
Background:
- Chronic unpredictable mild stress (CUMS) is a common model for inducing depressive-like behaviors in rodents.
- The glutamate (Glu)/metabotropic glutamate receptor 3 (mGluR3)/brain-derived neurotrophic factor (BDNF) signaling pathway is implicated in depression.
- Acupuncture is a traditional therapy with potential antidepressant effects, but its molecular mechanisms require further elucidation.
Purpose of the Study:
- To investigate the efficacy of acupuncture in alleviating CUMS-induced depressive-like behaviors in rats.
- To examine the involvement of the Glu/mGluR3/BDNF signaling pathway in acupuncture's antidepressant effects.
- To identify mGluR3 as a potential molecular substrate in this pathway.
Main Methods:
- Male Sprague-Dawley rats were subjected to the CUMS protocol to induce depression.
- Behavioral tests (OFT, FST, EPM, SPT) assessed depressive-like behaviors.
- Prefrontal cortex (PFC) tissue was analyzed for astrocyte density, and protein/gene expression of key molecules (EAAT1, GAD67, GAD65, GIRK2, BDNF, mGluR3) using Western blot and RT-PCR.
Main Results:
- Acupuncture significantly improved sucrose preference, increased exploration, and reduced immobility in CUMS rats.
- Acupuncture upregulated EAAT1, GABA, and BDNF expression while downregulating GAD65, GAD67, Glu, and mGluR3 in the PFC.
- The beneficial effects of acupuncture were diminished by sham acupuncture and mGluR3 antagonist treatments.
Conclusions:
- Acupuncture effectively ameliorates depressive-like behaviors in a rat model of depression.
- Therapeutic effects are associated with enhanced astrocyte activity, reduced glutamate toxicity in the PFC, and modulation of the Glu-mGluR3-BDNF pathway.
- mGluR3 is identified as a potential molecular substrate linked to acupuncture's antidepressant effects, warranting further investigation into its causal role.

