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Cited by 138Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsInflammasome and immune disorders

Outer membrane vesicles of Porphyromonas gingivalis trigger NLRP3 inflammasome and induce neuroinflammation, tau phosphorylation, and memory dysfunction in mice

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Gong, Ting, Chen, Qi, Mao, Hongchen, Zhang, Yao, Ren, Huan, Xu, Mengmeng, Chen, Hong, Yang, Deqin·2022·Frontiers in Cellular and Infection Microbiology
DOI 10.3389/fcimb.2022.925435PMC PMC9397999
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Abstract

Background: Porphyromonas gingivalis (Pg), the keystone pathogen in chronic periodontitis, is reported to initiate Alzheimer’s disease pathologies in preclinical studies. However, the specific mechanisms and signaling pathways acting on the brain still need to be further explored. Outer membrane vesicles are derived from Gram-negative bacteria and contain many virulence factors of bacteria. We hypothesized that outer membrane vesicles are an important weapon of Porphyromonas gingivalis to initiate Alzheimer’s disease pathologies. Methods: The outer membrane vesicles of Porphyromonas gingivalis (Pg OMVs, 4 mg/kg) or saline were delivered to 14-month-old mice by oral gavage every other day for eight weeks. Behavioral alterations were assessed by the open field test, Morris water maze, and Y-maze test. Blood–brain barrier permeability, neuroinflammation, tau phosphorylation, and NLRP3 inflammasome-related protein were analyzed. Results: Pg OMVs impaired memory and learning ability of mice and decreased tight junction–related gene expression ZO-1, occludin, claudin-5, and occludin protein expression in the hippocampus. Pg OMVs could be detected in the hippocampus and cortex three days after oral gavage. Furthermore, Pg OMVs activated both astrocytes and microglia and elevated IL-1β, tau phosphorylation on the Thr231 site, and NLRP3 inflammasome–related protein expression in the hippocampus. In in vitro studies, Pg OMV (5 µg/ml) stimulation increased the mRNA and immunofluorescence of NLRP3 in BV2 microglia, which were significantly inhibited by the NLRP3 inhibitor MCC950. In contrast, the tau phosphorylation in N2a neurons was enhanced after treatment with conditioned media from Pg OMV-stimulated microglia, which was attenuated after pretreatment with MCC950. Conclusions: These results indicate that Pg OMVs prompt memory dysfunction, neuroinflammation, and tau phosphorylation and trigger NLRP3 inflammasome in the brain of middle-aged mice. We propose that Pg OMVs play an important role in activating neuroinflammation in the AD-like pathology triggered by Porphyromonas gingivalis, and NLRP3 inflammasome activation is a possible mechanism.

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  • There is a strong epidemiologic association between periodontitis and Alzheimer's disease and related dementia.

    “There is a strong epidemiologic association between periodontitis (PD) and ADRD [5,6,7,8,9,10,11,12,13] but how these two diseases intersect and whether it is at the level of causation is unclear.”

    From Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier (2024) · cites this paper as [9]

    The Introduction (page unavailable) says epidemiological studies propose that periodontal disease is a risk factor for Alzheimer’s disease, supporting an epidemiologic association. It does not characterize the association as strong or extend it to other related dementias. (LLM, conf=0.83)

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References 74 · Cited by 138

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  1. Amano A. Takeuchi H. Furuta N. (2010). Outer membrane vesicles function as offensive weapons in host-parasite interactions. Microbes Infect. 12, 791– 798. doi: 10.1016/j.micinf.2010.05.008 20685339 · DOI
  2. Beyer M. M. S. Lonnemann N. Remus A. Latz E. Heneka M. T. Korte M. (2020). Enduring changes in neuronal function upon systemic inflammation are NLRP3 inflammasome dependent. J. Neurosci. 40, 5480– 5494. doi: 10.1523/JNEUROSCI.0200-20.2020 32499379 PMC7343321 · DOI · Paper page
  3. Bittel M. Reichert P. Sarfati I. Dressel A. Leikam S. Uderhardt S.. (2021). Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo. J. Extracell Vesicles. 10, e12159. doi: 10.1002/jev2.12159 34664784 PMC8524437 · DOI
  4. Boutaga K. Savelkoul P. H. Winkel E. G. van Winkelhoff A. J. (2007). Comparison of subgingival bacterial sampling with oral lavage for detection and quantification of periodontal pathogens by real-time polymerase chain reaction. J. Periodontol. 78, 9– 86. doi: 10.1902/jop.2007.060078 17199543 · DOI
  5. Cecil J. D. O'Brien-Simpson N. M. Lenzo J. C. Holden J. A. Singleton W. Perez-Gonzalez A.. (2017). Outer membrane vesicles prime and activate macrophage inflammasomes and cytokine secretion In vitro and In vivo. Front. Immunol. 8. doi: 10.3389/fimmu.2017.01017 PMC5574916 28890719 · DOI
  6. Chi L. Cheng X. Lin L. Yang T. Sun J. Feng Y.. (2021). Porphyromonas gingivalis induced cognitive impairment is associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction. Front. Cell Infect. Microbiol. 11. doi: 10.3389/fcimb.2021.755925 PMC8672439 34926316 · DOI
  7. Darveau R. P. Hajishengallis G. Curtis M. A. (2012). Porphyromonas gingivalis as a potential community activist for disease. J. Dent. Res. 91,9, 816– 820. doi: 10.1177/0022034512453589 22772362 PMC3420389 · DOI
  8. Deniz-Naranjo M. C. Munoz-Fernandez C. Alemany-Rodriguez M. J. Perez-Vieitez M. C. Aladro-Benito Y. Irurita-Latasa J.. (2008). Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the canary islands, Spain. Eur. J. Neurol. 15, 1080– 1084. doi: 10.1111/j.1468-1331.2008.02252.x 18717723 · DOI
  9. Ding Y. Ren J. Yu H. Yu W. Zhou Y. (2018). Porphyromonas gingivalis, a periodontitis causing bacterium, induces memory impairment and age-dependent neuroinflammation in mice. Immun. Ageing. 15, 6. doi: 10.1186/s12979-017-0110-7 29422938 PMC5791180 · DOI
  10. Doulberis M. Papaefthymiou A. Polyzos S. A. Boziki M. Deretzi G. Giartza-Taxidou E.. (2019). Microbes and alzheimer' disease: lessons from h. pylori and GUT microbiota. Eur. Rev. Med. Pharmacol. Sci. 23, 1845– 1846. doi: 10.26355/eurrev_201903_17218 30915725 · DOI
  11. Emery D. C. Shoemark D. K. Batstone T. E. Waterfall C. M. Coghill J. A. Cerajewska T. L.. (2017). 16S rRNA next generation sequencing analysis shows bacteria in alzheimer's post-mortem brain. Front. Aging Neurosci. 9. doi: 10.3389/fnagi.2017.00195 PMC5476743 28676754 · DOI · Paper page
  12. Fleetwood A. J. Lee M. K. S. Singleton W. Achuthan A. Lee M. C. O'Brien-Simpson N. M.. (2017). Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles. Front. Cell Infect. Microbiol. 7. doi: 10.3389/fcimb.2017.00351 PMC5543041 28824884 · DOI
  13. Franklin B. S. Bossaller L. De Nardo D. Ratter J. M. Stutz A. Engels G.. (2014). The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation. Nat. Immunol. 15, 727– 737. doi: 10.1038/ni.2913 24952505 PMC4116676 · DOI · Paper page
  14. Giovannini M. G. Lana D. Traini C. Vannucchi M. G. (2021). The microbiota-Gut-Brain axis and Alzheimer disease. from dysbiosis to neurodegeneration: Focus on the central nervous system glial cells. J. Clin. Med. 10, 2358. doi: 10.3390/jcm10112358 34072107 PMC8199461 · DOI
  15. Griffin W. S. Nicoll J. A. Grimaldi L. M. Sheng J. G. Mrak R. E. (2000). The pervasiveness of interleukin-1 in alzheimer pathogenesis: a role for specific polymorphisms in disease risk. Exp. Gerontol. 35, 481– 487. doi: 10.1016/s0531-5565(00)00110-8 10959036 PMC3833595 · DOI
  16. Gui M. J. Dashper S. G. Slakeski N. Chen Y. Y. Reynolds E. C. (2016). Spheres of influence: Porphyromonas gingivalis outer membrane vesicles. Mol. Oral. Microbiol. 31, 365– 378. doi: 10.1111/omi.12134 26466922 · DOI
  17. Gu Y. Wu Z. Zeng F. Jiang M. Teeling J. L. Ni J.. (2020). Systemic exposure to lipopolysaccharide from Porphyromonas gingivalis induces bone loss-correlated alzheimer's disease-like pathologies in middle-aged mice. J. Alzheimers Dis. 78, 61– 74. doi: 10.3233/JAD-200689 32925065 · DOI
  18. Ha J. Y. Choi S. Y. Lee J. H. Hong S. H. Lee H. J. (2020). Delivery of periodontopathogenic extracellular vesicles to brain monocytes and microglial IL-6 promotion by RNA cargo. Front. Mol. Biosci. 7. doi: 10.3389/fmolb.2020.596366 PMC7732644 33330627 · DOI
  19. Han E. C. Choi S. Y. Lee Y. Park J. W. Hong S. H. Lee H. J. (2019). Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-alpha production in human macrophages and cross the blood-brain barrier in mice. FASEB J. 33, 13412– 13422. doi: 10.1096/fj.201901575R 31545910 PMC6894046 · DOI
  20. Hao X. Li Z. Li W. Katz J. Michalek S. M. Barnum S. R.. (2022). Periodontal infection aggravates C1q-mediated microglial activation and synapse pruning in alzheimer’s mice. Front. Immunol. 13. doi: 10.3389/fimmu.2022.816640 PMC8845011 35178049 · DOI
  21. Hayashi K. Hasegawa Y. Takemoto Y. Cao C. Takeya H. Komohara Y.. (2019). Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of alzheimer's disease. Exp. Gerontol. 120, 1– 5. doi: 10.1016/j.exger.2019.02.007 30786259 · DOI
  22. He J. Huang W. Pan Z. Cui H. Qi G. Zhou X.. (2012). Quantitative analysis of microbiota in saliva, supragingival, and subgingival plaque of Chinese adults with chronic periodontitis. Clin. Oral. Investig. 16, 1579– 1588. doi: 10.1007/s00784-011-0654-4 22169888 · DOI
  23. Ho M. H. Guo Z. M. Chunga J. Goodwin J. S. Xie H. (2016). Characterization of innate immune responses of human endothelial cells induced by Porphyromonas gingivalis and their derived outer membrane vesicles. Front. Cell Infect. Microbiol. 6. doi: 10.3389/fcimb.2016.00139 PMC5078693 27826542 · DOI
  24. Hu Y. Li H. Zhang J. Zhang X. Xia X. Qiu C.. (2020). Periodontitis induced by p. gingivalis-LPS is associated with neuroinflammation and learning and memory impairment in sprague-dawley rats. Front. Neurosci. 14. doi: 10.3389/fnins.2020.00658 PMC7344110 32714134 · DOI
  25. Jiang M. Zhang X. Yan X. Mizutani S. Kashiwazaki H. Ni J.. (2021). GSK3beta is involved in promoting alzheimer's disease pathologies following chronic systemic exposure to Porphyromonas gingivalis lipopolysaccharide in amyloid precursor protein(NL-F/NL-F) knock-in mice. Brain Behav. Immun. 98, 1– 12. doi: 10.1016/j.bbi.2021.08.213 34391814 PMC8849844 · DOI
  26. Kato T. Yamazaki K. Nakajima M. Date Y. Kikuchi J. Hase K.. (2018). Oral administration of Porphyromonas gingivalis alters the gut microbiome and serum metabolome. mSphere 3, e00460–18. doi: 10.1128/mSphere.00460-18 PMC6193602 30333180 · DOI
  27. Keaney J. Campbell M. (2015). The dynamic blood-brain barrier. FEBS J. 282, 4067– 4079. doi: 10.1111/febs.13412 26277326 · DOI · Paper page
  28. Kovacech B. Novak M. (2010). Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in alzheimer's disease. Curr. Alzheimer Res. 7, 708– 716. doi: 10.2174/156720510793611556 20678071 · DOI
  29. Lee K. E. Kim J. K. Han S. K. Lee D. Y. Lee H. J. Yim S. V.. (2020). The extracellular vesicle of gut microbial paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment. Microbiome 8, 107. doi: 10.1186/s40168-020-00881-2 32669127 PMC7364628 · DOI
  30. Lei Y. Chen C. J. Yan X. X. Li Z. Deng X. H. (2017). Early-life lipopolysaccharide exposure potentiates forebrain expression of NLRP3 inflammasome proteins and anxiety-like behavior in adolescent rats. Brain Res. 1671, 43– 54. doi: 10.1016/j.brainres.2017.06.014 28655515 · DOI
  31. Lempriere S. (2020). NEURODEGENERATIVE DISEASE NLRP3 inflammasome activation implicated in tau pathology. Nat. Rev. Neurol. 16, 4. doi: 10.1038/s41582-019-0299-5 31811274 · DOI · Paper page
  32. Mantri C. K. Chen C. H. Dong X. Goodwin J. S. Pratap S. Paromov V.. (2015). Fimbriae-mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis. Microbiologyopen 4, 53– 65. doi: 10.1002/mbo3.221 25524808 PMC4335976 · DOI
  33. Nakajima M. Arimatsu K. Kato T. Matsuda Y. Minagawa T. Takahashi N.. (2015). Oral administration of p. gingivalis induces dysbiosis of gut microbiota and impaired barrier function leading to dissemination of enterobacteria to the liver. PloS One 10, e0134234. doi: 10.1371/journal.pone.0134234 26218067 PMC4517782 · DOI
  34. Nara P. L. Sindelar D. Penn M. S. Potempa J. Griffin W. S. T. (2021). Porphyromonas gingivalis outer membrane vesicles as the major driver of and explanation for neuropathogenesis, the cholinergic hypothesis, iron dyshomeostasis, and salivary lactoferrin in alzheimer's disease. J. Alzheimers Dis. 82, 1417– 1450. doi: 10.3233/JAD-210448 34275903 PMC8461682 · DOI · Paper page
  35. Neddens J. Temmel M. Flunkert S. Kerschbaumer B. Hoeller C. Loeffler T.. (2018). Phosphorylation of different tau sites during progression of alzheimer's disease. Acta Neuropathol. Commun. 6, 52. doi: 10.1186/s40478-018-0557-6 29958544 PMC6027763 · DOI · Paper page
  36. Nie R. Wu Z. Ni J. Zeng F. Yu W. Zhang Y.. (2019). Porphyromonas gingivalis infection induces amyloid-beta accumulation in Monocytes/Macrophages. J. Alzheimers Dis. 72, 479– 494. doi: 10.3233/JAD-190298 31594220 · DOI
  37. Noble J. M. Scarmeas N. Celenti R. S. Elkind M. S. Wright C. B. Schupf N.. (2014). Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease. PloS One 9, e114959. doi: 10.1371/journal.pone.0114959 25522313 PMC4270775 · DOI
  38. Nonaka S. Kadowaki T. Nakanishi H. (2022). Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins. Neurochem. Int. 154, 105282. doi: 10.1016/j.neuint.2022.105282 35032577 · DOI · Paper page
  39. Oprica M. Hjorth E. Spulber S. Popescu B. O. Ankarcrona M. Winblad B.. (2007). Studies on brain volume, Alzheimer-related proteins and cytokines in mice with chronic overexpression of IL-1 receptor antagonist. J. Cell Mol. Med. 11, 810– 825. doi: 10.1111/j.1582-4934.2007.00074.x 17760842 PMC3823259 · DOI
  40. Pickering M. O'Connor J. J. (2007). Pro-inflammatory cytokines and their effects in the dentate gyrus. Dentate. Gyrus.: A Comphrehens. Guide. To. Struct. Function. Clin. Implicat. 163, 339– 354. doi: 10.1016/S0079-6123(07)63020-9 17765728 · DOI · Paper page
  41. Poole S. Singhrao S. K. Kesavalu L. Curtis M. A. Crean S. (2013). Determining the presence of periodontopathic virulence factors in short-term postmortem alzheimer's disease brain tissue. J. Alzheimers Dis. 36, 665– 677. doi: 10.3233/JAD-121918 23666172 · DOI
  42. Pritchard A. B. Fabian Z. Lawrence C. L. Morton G. Crean S. Alder J. E. (2022). An investigation into the effects of outer membrane vesicles and lipopolysaccharide of Porphyromonas gingivalis on blood-brain barrier integrity, permeability, and disruption of scaffolding proteins in a human in vitro model. J. Alzheimers Dis. 86, 343– 364. doi: 10.3233/JAD-215054 35034897 · DOI
  43. Qian X. Zhang S. Duan L. Yang F. Zhang K. Yan F.. (2021). Periodontitis deteriorates cognitive function and impairs neurons and glia in a mouse model of alzheimer's disease. J. Alzheimers Dis. 79, 1785– 1800. doi: 10.3233/JAD-201007 33459718 · DOI
  44. Reimers D. Vallejo-Munoz M. Casarejos M. J. Jimenez-Escrig A. Gonzalo-Gobernado R. Bazan E. (2021). Immunohistochemical study of ASC expression and distribution in the hippocampus of an aged murine model of alzheimer's disease. Int. J. Mol. Sci. 22, 8697. doi: 10.3390/ijms22168697 34445402 PMC8395512 · DOI
  45. Ryder M. I. (2020). Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies. J. Periodontol. 91 Suppl 1, S45– S49. doi: 10.1002/JPER.20-0104 32533852 PMC7689719 · DOI
  46. Saygun I. Nizam N. Keskiner I. Bal V. Kubar A. Acikel C.. (2011). Salivary infectious agents and periodontal disease status. J. Periodontal. Res. 46, 235– 239. doi: 10.1111/j.1600-0765.2010.01335.x 21261620 · DOI
  47. Schertzer J. W. Whiteley M. (2013). Bacterial outer membrane vesicles in trafficking, communication and the host-pathogen interaction. J. Mol. Microbiol. Biotechnol. 23, 118– 130. doi: 10.1159/000346770 23615200 · DOI
  48. Schroder K. Tschopp J. (2010). The inflammasomes. Cell 140, 821– 832. doi: 10.1016/j.cell.2010.01.040 20303873 · DOI · Paper page
  49. Seyama M. Yoshida K. Yoshida K. Fujiwara N. Ono K. Eguchi T.. (2020). Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver. Biochim. Biophys. Acta Mol. Bas. Dis. 1866, 165731. doi: 10.1016/j.bbadis.2020.165731 32088316 · DOI
  50. Sheng J. G. Zhu S. G. Jones R. A. Griffin W. S. Mrak R. E. (2000). Interleukin-1 promotes expression and phosphorylation of neurofilament and tau proteins in vivo. Exp. Neurol. 163, 388– 391. doi: 10.1006/exnr.2000.7393 10833312 PMC3886634 · DOI
  51. Singhrao S. K. Olsen I. (2018). Are Porphyromonas gingivalis outer membrane vesicles microbullets for sporadic alzheimer's disease manifestation? J. Alzheimers Dis. Rep. 2, 219– 228. doi: 10.3233/adr-180080 30599043 PMC6311351 · DOI
  52. Sparks Stein P. Steffen M. J. Smith C. Jicha G. Ebersole J. L. Abner E.. (2012). Serum antibodies to periodontal pathogens are a risk factor for alzheimer's disease. Alzheimers Dement. 8, 196– 203. doi: 10.1016/j.jalz.2011.04.006 22546352 PMC3712346 · DOI
  53. Su X. Y. Tang Z. Q. Lu Z. Y. Liu Y. Q. He W. Z. Jiang J. P.. (2021). Oral treponema denticola infection induces a beta(1-40) and a beta(1-42) accumulation in the hippocampus of C57BL/6 mice. J. Mol. Neurosci. 71, 1506– 1514. doi: 10.1007/s12031-021-01827-5 33763842 · DOI
  54. Tang Z. Liang D. Cheng M. Su X. Liu R. Zhang Y.. (2021). Effects of Porphyromonas gingivalis and its underlying mechanisms on Alzheimer-like tau hyperphosphorylation in sprague-dawley rats. J. Mol. Neurosci. 71, 89– 100. doi: 10.1007/s12031-020-01629-1 32557144 · DOI
  55. Tan M. S. Yu J. T. Jiang T. Zhu X. C. Tan L. (2013). The NLRP3 inflammasome in alzheimer's disease. Mol. Neurobiol. 48, 875– 882. doi: 10.1007/s12035-013-8475-x 23686772 · DOI
  56. Toyofuku M. Nomura N. Eberl L. (2019). Types and origins of bacterial membrane vesicles. Nat. Rev. Microbiol. 17, 13– 24. doi: 10.1038/s41579-018-0112-2 30397270 · DOI
  57. Wei S. Peng W. Mai Y. Li K. Wei W. Hu L.. (2020). Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment. J. Cell Physiol. 235, 4843– 4855. doi: 10.1002/jcp.29362 31663118 · DOI
  58. Wen H. Miao E. A. Ting J. P. (2013). Mechanisms of NOD-like receptor-associated inflammasome activation. Immunity 39, 432– 441. doi: 10.1016/j.immuni.2013.08.037 24054327 PMC3835203 · DOI
  59. Wu Z. Ni J. Liu Y. Teeling J. L. Takayama F. Collcutt A.. (2017). Cathepsin b plays a critical role in inducing alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav. Immun. 65, 350– 361. doi: 10.1016/j.bbi.2017.06.002 28610747 · DOI
  60. Xue L. Zou X. Yang X. Q. Peng F. Yu D. K. Du J. R. (2020). Chronic periodontitis induces microbiota-gut-brain axis disorders and cognitive impairment in mice. Exp. Neurol. 326, 113176. doi: 10.1016/j.expneurol.2020.113176 31926167 · DOI
  61. Zihni C. Mills C. Matter K. Balda M. S. (2016). Tight junctions: from simple barriers to multifunctional molecular gates. Nat. Rev. Mol. Cell Biol. 17, 564– 580. doi: 10.1038/nrm.2016.80 27353478 · DOI

Authors
Gong, T., Chen, Q., Mao, H., Zhang, Y., Ren, H., Xu, M., Chen, H., & Yang, D.
Affiliations
Stomatological Hospital of Chongqing Medical University (CN)
Corresponding author
Yang, Deqin
ORCID
Venue
Frontiers in Cellular and Infection Microbiology
Publisher
Frontiers Media SA
Published
2022-08-09
Volume
12
Pages
925435-925435
ISSN
2235-2988 (ISSN-L)
DOI
10.3389/fcimb.2022.925435
PMC
PMC9397999
OpenAlex
W4290730903
Cited by
138
References
74
Citations by year
2026: 39 · 2025: 44 · 2024: 36 · 2023: 19
FWCI
15.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Chongqing Medical University (W0060)
  • Natural Science Foundation of Chongqing (cstc2021jcyj)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
Porphyromonas gingivalis, outer membrane vesicles, NLRP3 inflammasome, neuroinflammation, tau phosphorylation, Alzheimer's disease, memory impairment, blood-brain barrier permeability, microglia, astrocytes, IL-1β, periodontitis, hippocampus, MCC950
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Neuroinflammatory Diseases, Alzheimer Disease, Phosphorylation, tau Proteins, Porphyromonas gingivalis, Inflammasomes, Occludin

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