IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease
Abstract Background Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deteriorat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02747-4 |
| _version_ | 1827983172920410112 |
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| author | Rachel Pei-Hsuan Wang Jianpan Huang Kannie Wai Yan Chan Wai Keung Leung Tetsuya Goto Yuen-Shan Ho Raymond Chuen-Chung Chang |
| author_facet | Rachel Pei-Hsuan Wang Jianpan Huang Kannie Wai Yan Chan Wai Keung Leung Tetsuya Goto Yuen-Shan Ho Raymond Chuen-Chung Chang |
| author_sort | Rachel Pei-Hsuan Wang |
| collection | DOAJ |
| description | Abstract Background Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer’s disease. With advancing age, the progressive increase in the body’s pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer’s disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases. Methods To examine the impacts of periodontitis on the onset and progression of Alzheimer’s disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer’s disease, interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice. Results Here, we show that IL-1β and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer’s disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer’s disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer’s disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice. Conclusions Systemic inflammation resulting from periodontitis contributed to the development of Alzheimer’s disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer’s disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer’s disease. |
| first_indexed | 2024-04-09T22:44:35Z |
| format | Article |
| id | doaj.art-2d3d094d296049d1aa043c8692284cb5 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-09T22:44:35Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-2d3d094d296049d1aa043c8692284cb52023-03-22T11:55:18ZengBMCJournal of Neuroinflammation1742-20942023-03-0120113010.1186/s12974-023-02747-4IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s diseaseRachel Pei-Hsuan Wang0Jianpan Huang1Kannie Wai Yan Chan2Wai Keung Leung3Tetsuya Goto4Yuen-Shan Ho5Raymond Chuen-Chung Chang6Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong KongDepartment of Biomedical Engineering, City University of Hong KongDepartment of Biomedical Engineering, City University of Hong KongFaculty of Dentistry, The University of Hong KongDivision of Oral Anatomy and Histology, Graduate School of Medical and Dental Sciences, Kagoshima UniversitySchool of Nursing, Faculty of Health and Social Sciences, Hong Kong Polytechnic UniversityLaboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong KongAbstract Background Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer’s disease. With advancing age, the progressive increase in the body’s pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer’s disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases. Methods To examine the impacts of periodontitis on the onset and progression of Alzheimer’s disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer’s disease, interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice. Results Here, we show that IL-1β and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer’s disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer’s disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer’s disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice. Conclusions Systemic inflammation resulting from periodontitis contributed to the development of Alzheimer’s disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer’s disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer’s disease.https://doi.org/10.1186/s12974-023-02747-4Alzheimer’s diseaseAgingCognitive dysfunctionsNeuroinflammationPeriodontitis |
| spellingShingle | Rachel Pei-Hsuan Wang Jianpan Huang Kannie Wai Yan Chan Wai Keung Leung Tetsuya Goto Yuen-Shan Ho Raymond Chuen-Chung Chang IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease Journal of Neuroinflammation Alzheimer’s disease Aging Cognitive dysfunctions Neuroinflammation Periodontitis |
| title | IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease |
| title_full | IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease |
| title_fullStr | IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease |
| title_full_unstemmed | IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease |
| title_short | IL-1β and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer’s disease |
| title_sort | il 1β and tnf α play an important role in modulating the risk of periodontitis and alzheimer s disease |
| topic | Alzheimer’s disease Aging Cognitive dysfunctions Neuroinflammation Periodontitis |
| url | https://doi.org/10.1186/s12974-023-02747-4 |
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