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Cited by 5Acupuncture Treatment Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

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Electroacupuncture promotes BDNF-dependent neurogenesis via microglial reprogramming in a chronic stress model

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Zhang, Lijuan, Wei, Ting, Liu, Xuan, Zhang, Lifan, Wang, Dan, Luo, Yucai, He, Yanyan, He, Zhaoxuan, Zeng, Fang·2026·Chinese Medicine
DOI 10.1186/s13020-026-01334-yPMC PMC12866076

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Abstract

Background: Aberrant microglial activation and impaired adult hippocampal neurogenesis play critical roles in the pathogenesis of depression. Although electroacupuncture (EA) has demonstrated clinical antidepressant efficacy, the underlying mechanisms by which it modulates microglial activity and promotes neurogenesis remain unclear. Methods: Male C57BL/6 J mice were subjected to chronic unpredictable mild stress (CUMS) for three weeks. Following this period, the mice were divided into groups receiving either EA at the Yintang (GV29) and Baihui (GV20) acupoints, imipramine (IMI) as a positive control, or no treatment (vehicle control) for an additional 3 weeks. To evaluate depressive-like behaviors, we conducted the sucrose preference test, forced swimming test, and tail suspension test. Anxiety-like behaviors were assessed using the open field test and elevated plus maze. We employed immunofluorescence, Golgi staining, Western blotting, and real-time quantitative PCR (qRT-PCR) to elucidate the effects of EA on microglia-driven hippocampal neurogenesis and BDNF signaling. Notably, loss-of-function experiments utilizing PLX5622 for microglial ablation and ANA-12 for TrkB blockade demonstrated the necessity of both microglia and BDNF signaling for the therapeutic efficacy of EA. Results: EA treatment significantly alleviated CUMS-induced anxiodepressive behaviors. This behavioral recovery was associated with a phenotypic shift in microglia towards a pro-neurogenic state in the hippocampus. Importantly, microglia were essential for the therapeutic effects of EA, as evidenced by their ablation with PLX5622. Furthermore, EA enhanced neurogenesis by orchestrating a multi-step augmentation of BDNF signaling, which involved PKA activation, subsequent release from MeCP2-mediated transcriptional repression, and ultimately increased maturation of BDNF. Conclusions: Our findings demonstrate that EA exerts antidepressant effects by promoting a pro-neurogenic transformation of microglia. Mechanistically, these microglia enhance BDNF function via the PKA/MeCP2/BDNF pathway, thereby facilitating hippocampal neurogenesis and restoring synaptic plasticity, which collectively alleviate depressive symptoms. Graphical Abstract:

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Metadata

Authors
Zhang, L., Wei, T., Liu, X., Zhang, L., Wang, D., Luo, Y., He, Y., He, Z., & Zeng, F.
Affiliations
  • Chengdu University (CN)
  • Chengdu University of Traditional Chinese Medicine (CN)
Corresponding author
Zeng, Fang
ORCID
Venue
Chinese Medicine
Publisher
Springer Science and Business Media LLC
Published
2026-02-03
Volume
21
Issue
1
Pages
62-62
ISSN
1749-8546 (ISSN-L)
DOI
10.1186/s13020-026-01334-y
PMC
PMC12866076
OpenAlex
W7127353409
Cited by
5
References
8
Citations by year
2026: 5
FWCI
52.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Chinese Medicine (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • China Postdoctoral Science Foundation (GZB20240088)
  • Sichuan Provincial Science and Technology Support Program (2024YFFK0161)
  • Sichuan Provincial Youth Science and Technology Foundation (23NSFSC6282)
  • National Natural Science Foundation of China (82225050)
  • Sichuan Province Tianfu Qingcheng Program
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Acupuncture Treatment Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
electroacupuncture, microglial reprogramming, adult hippocampal neurogenesis, BDNF signaling, chronic unpredictable mild stress, depression, anxiety, PLX5622, ANA-12, TrkB, MeCP2, pKa, antidepressant effects, Baihui (GV20)

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