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Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve

  • Acupuncture Research
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice.

Methods

Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively.

Results

Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01).

Conclusions

OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer’s disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota.

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Author information

Authors and Affiliations

  1. College of Acu-moxibustion and Massage, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China

    Yuan Wang, Qiang Wang, Biao Dai, Jia-ju Wang, Yi-tong Wan & Zhi-bin Liu

  2. Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712046, China

    Yuan Wang, A.-ni Zheng, Qiang Wang & Zhi-bin Liu

  3. The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, 712000, China

    A.-ni Zheng

  4. Department of Traditional Chinese Medicine, Baotou Medical College, Baotou, Inner Mongolia Autonomous Region, 014040, China

    Huan Yang

  5. School of Basic Medical Sciences, Xi’an Medical University, Xi’an, 710021, China

    Si-yang Liu

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  1. Yuan Wang
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  2. A.-ni Zheng
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  3. Huan Yang
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  4. Qiang Wang
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  9. Si-yang Liu
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Contributions

Wang Y and Liu SY designed the experiments. Wang Y, Zheng AN, Yang H, and Wang Q performed the experiments. Dai B and Wang JJ analyzed the data. Wan YT and Liu ZB contributed to the reagents and materials. Wang Y wrote the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Si-yang Liu.

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The authors declare that they have no competing interests.

Additional information

Supported by the National Natural Science Foundation of China (No. 82074552), the Shaanxi Science and Technology Department Project (No. 2018JM7041), and Shaanxi Province TCM “Double Chain Integration” Young and Middle-Aged Scientific Research Innovation Team Construction Project (No. 2022-SLRH-LJ-012)

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Wang, Y., Zheng, An., Yang, H. et al. Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve. Chin. J. Integr. Med. (2023). https://doi.org/10.1007/s11655-023-3614-3

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  • DOI: https://doi.org/10.1007/s11655-023-3614-3

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