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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.
Objective:
The present study investigated whether acupuncture alleviates CUMS-induced depressive-like behaviors in rats and examined whether the Glu-mGluR3-BDNF signaling pathway is associated with these effects, identifying mGluR3 as a potential molecular correlate rather than a confirmed causal mediator.
Methods:
Male Sprague-Dawley (SD) rats were randomly allocated into six groups: Control, CUMS, CUMS + FXT, CUMS + AP, CUMS + SAP, and CUMS + RA. Depression was induced using the CUMS protocol. Behavioral assessments, including the OFT, FST, EPM, and SPT, were conducted to evaluate depressive-like behaviors. Histological examination of the prefrontal cortex (PFC) was performed using Hematoxylin, Eosin, and Nissl staining, while immunofluorescence was employed to quantify astrocyte density within this region. Protein and gene expressions of EAAT1, GAD67, GAD65, GIRK2, BDNF, and mGluR3 in the PFC tissue were quantified using Western blot and RT-PCR, respectively.
Results:
After 28 days of CUMS, rats in the CUMS group exhibited a significant reduction in body weight compared to Controls. After 21 days of intervention, acupuncture significantly enhanced sucrose preference, increased central zone occupancy in the OFT, and reduced immobility time in the FST relative to the CUMS group. At the molecular level, acupuncture markedly upregulated EAAT1, GABA, and BDNF expression and concurrently downregulated GAD65, GAD67, Glu, and mGluR3 levels. Notably, these beneficial effects were significantly attenuated in the sham acupuncture and mGluR3 agonist groups.
Conclusion:
Acupuncture ameliorates core depressive-like behaviors in CUMS rats. These therapeutic effects are accompanied by enhanced astrocyte activity and mitigated glutamate toxicity in the prefrontal cortex (PFC), and were associated with coordinated changes in the Glu-mGluR3-BDNF signaling pathway. Within this pathway, mGluR3 emerged as a potential molecular substrate linked to the antidepressant-like response to acupuncture; however, its causal role and cell-type-specific regulation remain to be validated in future studies.
