2. Academic Validation
  3. Sleep Deprivation Aggravates Periodontitis Through Trigeminal-Periodontal Neuroimmune Pathway Mediated by the AChE-ACh-α7nAChR Axis

Sleep Deprivation Aggravates Periodontitis Through Trigeminal-Periodontal Neuroimmune Pathway Mediated by the AChE-ACh-α7nAChR Axis

  • Adv Sci (Weinh). 2025 Aug 14:e00945. doi: 10.1002/advs.202500945.
Kehao Liu 1,  Qi Huang 1,  Mingcong Yang 1,  Ziyu Huang 1,  Kamoran Tuerhong 1,  Yue Zu 1,  Ying Xie 1,  Xuehui Hu 1,  Qianyu Zhang 1,  Ping He 1,  Nannan Huang 1,  Rong Zhang 2 3 4 5 6,  Yuzhou Li 1 7,  Sheng Yang 1 7
Affiliations

Affiliations

  • 1 College of Stomatology, Chongqing Medical University, Chongqing, 401147, P. R. China.
  • 2 Neuroscience Research Institute, Peking University, Beijing, 100871, P. R. China.
  • 3 Department of Neurobiology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100871, P. R. China.
  • 4 Key Laboratory for Neuroscience, Ministry of Education, Key Laboratory for Neuroscience, Ministry of Health, Beijing, 100871, P. R. China.
  • 5 Autism Research Center of Peking University Health Science Center, Beijing, 100871, P. R. China.
  • 6 Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100871, P. R. China.
  • 7 Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, P. R. China.
PMID: 40810704 DOI: 10.1002/advs.202500945
Abstract

Continuous sleep deprivation (SD) triggers systemic inflammatory storm and immune dysregulation, yet its specific impact on periodontitis and the corresponding therapeutic interventions remains unclear. Consequently, this study elucidates the neuroimmune mechanisms linking SD to ligature-induced periodontitis (LIP) in mice and evaluates electroacupuncture (EA) as a novel adjunctive therapy. Screening analyses (ELISA, public databases, flow cytometry, immunofluorescence, etc.) identified pivotal roles of acetylcholine (ACh), α7 nicotinic acetylcholine receptor (α7nAChR), and acetylcholinesterase (AChE) in SD-aggravated periodontitis with a decrease in ACh levels, down-regulation of α7nAChR on macrophages, and an increase in trigeminal ganglion-derived AChE. Clinical validation in periodontitis patients with poor sleep (PSQI ≥ 5) confirmed this tripartite cholinergic imbalance. Ultimately, both in vivo and in vitro data demonstrated that EA inhibits M1 polarization while promoting M2 polarization of macrophages through α7nAChR activation. Therefore, SD exacerbates periodontitis via the AChE-ACh-α7nAChR axis-mediated trigeminal-periodontal neuroimmune pathway, whereas EA partially reverses this pathology by targeting macrophage α7nAChR. These findings reveal new insights into the "oral-brain axis" in oral disease pathogenesis and provide novel therapeutic strategies for periodontitis patients with comorbid sleep disorders.

Keywords

cholinergic anti‐inflammatory pathway; electroacupuncture; macrophage; neuroimmune; periodontitis; sleep deprivation; α7nAChR.

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