Acupuncture ameliorates neurodamage in STZ-induced AD rat model, accompanied by BNIP3/NIX-related mitophagy signals
5 affiliations
- 1Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518000, China
- 2Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518000, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510180, China
- 3Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518000, China; Shenzhen TCM Anorectal Hospital (Futian), Shenzhen, 518049, China
- 4Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100000, China
- 5Beijing University of Chinese Medicine Shenzhen Hospital (Longgang), Shenzhen, 518000, China; Corresponding author.
Abstract
Background: Mitochondrial dysfunction and defective mitophagy are closely tied to the pathology of Alzheimer's disease (AD). Although acupuncture exerts neuroprotective effects in AD, whether it acts via BNIP3/NIX-mediated mitophagy remains unclear. Methods: Male Sprague-Dawley rats underwent ICV streptozotocin (STZ) modeling and were evaluated after 7, 14, or 21 days of acupuncture at GV20, GV22, and bilateral GB20, with or without Mdivi-1. After acupuncture intervention, spatial learning performance was evaluated with the Morris water maze (MWM) acquisition task. The mitophagy-related mechanisms underlying the therapeutic effects were investigated via TUNEL staining, transmission electron microscopy (TEM), western blotting, and double immunofluorescence. Results: In the Morris water maze test, acupuncture intervention markedly shortened the escape latency of AD rats. TUNEL staining revealed a reduction in TUNEL-positive cells in the hippocampus following acupuncture treatment. TEM demonstrated that acupuncture alleviated mitochondrial ultrastructural abnormalities in the hippocampal region. Western blotting demonstrated that acupuncture increased HIF-1α, BNIP3, and LC3 protein expression, while downregulating caspase-3. Double immunofluorescence staining revealed enhanced co-localization of LC3 and combined BNIP3/NIX lableling in the acupuncture group. Moreover, administration of Mdivi-1 exacerbated cognitive dysfunction, partially reversed the neuroprotective effects, and attenuated the upregulation of BNIP3 and LC3. Conclusion: Acupuncture exerts neuroprotective effects in this AD rat model, at least in part, through activation of mitophagy-related signaling potentially involving BNIP3/NIX.
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BibTeX
@article{ling2026acupuncture,
title = {{Acupuncture ameliorates neurodamage in STZ-induced AD rat model, accompanied by BNIP3/NIX-related mitophagy signals}},
author = {Zhenzhen Ling and Xin Wang and Boling Li and Yonglie Zhao and Beng Zhang and Xiaoqing Zhou},
journal = {Journal of Radiation Research and Applied Sciences},
year = {2026},
month = oct,
doi = {10.1016/j.jrras.2026.102776},
url = {https://doi.org/10.1016/j.jrras.2026.102776},
note = {CC BY},
}
RIS
TY - JOUR
TI - Acupuncture ameliorates neurodamage in STZ-induced AD rat model, accompanied by BNIP3/NIX-related mitophagy signals
AU - Zhenzhen Ling
AU - Xin Wang
AU - Boling Li
AU - Yonglie Zhao
AU - Beng Zhang
AU - Xiaoqing Zhou
PY - 2026
DA - 2026/10/30
JO - Journal of Radiation Research and Applied Sciences
DO - 10.1016/j.jrras.2026.102776
UR - https://doi.org/10.1016/j.jrras.2026.102776
AB - Background: Mitochondrial dysfunction and defective mitophagy are closely tied to the pathology of Alzheimer's disease (AD). Although acupuncture exerts neuroprotective effects in AD, whether it acts via BNIP3/NIX-mediated mitophagy remains unclear. Methods: Male Sprague-Dawley rats underwent ICV streptozotocin (STZ) modeling and were evaluated after 7, 14, or 21 days of acupuncture at GV20, GV22, and bilateral GB20, with or without Mdivi-1. After acupuncture intervention, spatial learning performance was evaluated with the Morris water maze (MWM) acquisition task. The mitophagy-related mechanisms underlying the therapeutic effects were investigated via TUNEL staining, transmission electron microscopy (TEM), western blotting, and double immunofluorescence. Results: In the Morris water maze test, acupuncture intervention markedly shortened the escape latency of AD rats. TUNEL staining revealed a reduction in TUNEL-positive cells in the hippocampus following acupuncture treatment. TEM demonstrated that acupuncture alleviated mitochondrial ultrastructural abnormalities in the hippocampal region. Western blotting demonstrated that acupuncture increased HIF-1α, BNIP3, and LC3 protein expression, while downregulating caspase-3. Double immunofluorescence staining revealed enhanced co-localization of LC3 and combined BNIP3/NIX lableling in the acupuncture group. Moreover, administration of Mdivi-1 exacerbated cognitive dysfunction, partially reversed the neuroprotective effects, and attenuated the upregulation of BNIP3 and LC3. Conclusion: Acupuncture exerts neuroprotective effects in this AD rat model, at least in part, through activation of mitophagy-related signaling potentially involving BNIP3/NIX.
SN - 2314-7164
SN - 1687-8507
ER -