{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:17:04Z","timestamp":1790381824927,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Trade, Industry&amp; Energy, the Technology Innovation Program","award":["NRF-2020R1A2C2010285, NRF-2018M3C7A1056896, MOTIE-20012352"],"award-info":[{"award-number":["NRF-2020R1A2C2010285, NRF-2018M3C7A1056896, MOTIE-20012352"]}]},{"name":"the Ministry of Science, ICT and Future Planning, the Bio &amp; Medical Technology Development Program","award":["NRF-2017M3A9E4047243"],"award-info":[{"award-number":["NRF-2017M3A9E4047243"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Porphyromonas gingivalis is a gram-negative bacterium found in the human oral cavity and is responsible for the development of chronic periodontitis as well as neurological diseases, including Alzheimer\u2019s disease (AD). Given the significance of the roles of P. gingivalis in AD pathogenesis, it is critical to understand the underlying mechanisms of P. gingivalis-driven neuroinflammation and their contribution to neurodegeneration. Herein, we hypothesize that P. gingivalis produces secondary metabolites that may cause neurodegeneration through direct or indirect pathways mediated by microglia. To test our hypothesis, we treated human neural cells with bacterial conditioned media on our brain platforms and assessed microgliosis, astrogliosis and neurodegeneration. We found that bacteria-mediated microgliosis induced the production of nitric oxide, which causes neurodegeneration assessed with high pTau level. Our study demonstrated the elevation of detrimental protein mediators, CD86 and iNOS and the production of several pro-inflammatory markers from stimulated microglia. Through inhibition of LPS and succinate dehydrogenase in a bacterial conditioned medium, we showed a decrease in neurodegenerative microgliosis. In addition, we demonstrated the bidirectional effect of microgliosis and astrogliosis on each other exacerbating neurodegeneration. Overall, our study suggests that the mouth-brain axis may contribute to the pathogenesis of AD.<\/jats:p>","DOI":"10.3390\/ijms22136925","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T11:45:40Z","timestamp":1624880740000},"page":"6925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Oral Pathogenic Bacteria-Inducing Neurodegenerative Microgliosis in Human Neural Cell Platform"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3521-6701","authenticated-orcid":false,"given":"Tran Thi Ai","family":"Tran","sequence":"first","affiliation":[{"name":"Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, NC 28223, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Kyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jeonbuk National University, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-2462","authenticated-orcid":false,"given":"Hyung-Ryong","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Dentistry, Dankook University, Choenan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hansang","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"History and progress of hypotheses and clinical trials for alzheimer\u2019s disease","volume":"4","author":"Liu","year":"2019","journal-title":"Signal. 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