Sleep deficiency exacerbates periodontal inflammation via trigeminal TRPV1 neurons
Periodontitis, a prevalent chronic inflammatory disease, profoundly impacts both quality of life and overall health. Clinical studies have suggested a correlation between periodontitis and sleep deficiency, but the underlying mechanisms involved remain elusive. Here, we observed an elevated risk of periodontitis in individuals with sleep deficiency, as demonstrated in both clinical subjects and mouse models. Retrograde tracing from the periodontium revealed a neural connection from trigeminal TRPV1 neurons, which may mediate the aggravating effects of sleep deficiency on periodontitis. The ablation of TRPV1 neurons effectively mitigated the aggravating effects of sleep deficiency on periodontitis. Under periodontitis, sleep restriction increased the secretion of substance P from trigeminal neurons in the periodontium, enhancing vasodilation and vascular permeability, which in turn promoted the infiltration of proinflammatory immune cells. Blocking substance P signaling via a Neurokinin-1 receptor antagonist or knocking down Tacr1 in vascular endothelial cells alleviated these detrimental effects. Our findings unveil a critical neuron-vessel-immune axis that exacerbates periodontitis during sleep deficiency and suggest potential therapeutic strategies targeting this axis for managing periodontitis in individuals suffering from sleep deficiency.
Authors
- Zhiyong Yuan (ORCID: https://orcid.org/0000-0002-4745-6895)
- Nan Zhou (ORCID: https://orcid.org/0000-0002-7996-6291)
- Junhui Li
- Chuanxin Huang (ORCID: https://orcid.org/0000-0003-2667-9587)
- Yao Sun (ORCID: https://orcid.org/0000-0002-4323-0506)
- Yao Zhao (ORCID: https://orcid.org/0000-0002-2932-2164)
- Yan Zhang (ORCID: https://orcid.org/0000-0002-8299-2220)
- Zhi Zhang (ORCID: https://orcid.org/0000-0002-3222-2877)
- Zi-Hao Zhang (ORCID: https://orcid.org/0009-0001-0191-1725)
- Xia Li (ORCID: https://orcid.org/0000-0001-7252-6907)
- Zengyi Ma (ORCID: https://orcid.org/0000-0002-6948-9049)
- Hongyu Gong (ORCID: https://orcid.org/0009-0008-3460-241X)
- Zhizhong Cui (ORCID: https://orcid.org/0009-0003-4254-2334)
Institutions
- Tongji University (CN)
- University of Science and Technology of China (CN)
- Henan University (CN)
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- Inner Mongolia University (CN)
- XinHua Hospital (CN)
- Ruijin Hospital (CN)
- Hefei National Center for Physical Sciences at Nanoscale (CN)
- Ministry of Education (TH)
- National Clinical Research (US)
- Institute of Immunology (HR)
- Huashan Hospital (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- State Key Laboratory of Medical Neurobiology
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1073/pnas.2424169122
- Citations
- 4
- Primary Topic
- Neuroscience of respiration and sleep
- Type
- article
- Field-Weighted Citation Impact
- 3.66
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Education and Scientific Research Project of Shanghai