triggers microglia activation and neurodegenerative processes through NOX4.

Anna Magnusson, Rongrong Wu, Isak Demirel
Author Information
  1. Anna Magnusson: School of Medical Sciences, ��rebro University, ��rebro, Sweden.
  2. Rongrong Wu: School of Medical Sciences, ��rebro University, ��rebro, Sweden.
  3. Isak Demirel: School of Medical Sciences, ��rebro University, ��rebro, Sweden.

Abstract

Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years, attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria and microglia cells and to unravel whether these interactions could contribute to the pathology of Alzheimer's disease. We found, through microarray analysis, that stimulation of microglia cells with resulted in the upregulation of several Alzheimer's disease-associated genes, including NOX4. We also showed that lipopolysaccharides (LPS) mediated reactive oxygen species (ROS) production and interleukin 6 (IL-6) and interleukin 8 (IL-8) induction via NOX4 in microglia. The viability of neurons was shown to be reduced by conditioned media from microglia cells stimulated with LPS and the reduction was NOX4 dependent. The levels of total and phosphorylated tau in neurons were increased by conditioned media from microglia cells stimulated with or LPS. This increase was NOX4-dependent. In summary, our findings provide us with a potential mechanistic explanation of how the periodontal pathogen could trigger or exacerbate AD pathogenesis.

Keywords

References

  1. J Clin Periodontol. 2018 Jun;45 Suppl 20:S162-S170 [PMID: 29926490]
  2. Neurochem Res. 2024 Apr;49(4):834-846 [PMID: 38227113]
  3. Alzheimers Res Ther. 2017 Aug 8;9(1):56 [PMID: 28784164]
  4. J Oral Microbiol. 2018 Feb 26;10(1):1440128 [PMID: 29503705]
  5. Physiol Rev. 2007 Jan;87(1):245-313 [PMID: 17237347]
  6. Sci Adv. 2019 Jan 23;5(1):eaau3333 [PMID: 30746447]
  7. Clin Dev Immunol. 2013;2013:325481 [PMID: 24371447]
  8. BMC Microbiol. 2009 May 27;9:107 [PMID: 19473524]
  9. PLoS One. 2018 Oct 3;13(10):e0204941 [PMID: 30281647]
  10. J Innate Immun. 2009;1(6):570-81 [PMID: 20375612]
  11. J Alzheimers Dis. 2020;75(1):157-172 [PMID: 32280099]
  12. Mol Neurobiol. 2018 Jan;55(1):619-632 [PMID: 27975175]
  13. Geroscience. 2024 Oct;46(5):4315-4332 [PMID: 38507186]
  14. Front Aging Neurosci. 2018 Feb 22;10:42 [PMID: 29520228]
  15. Sci Rep. 2017 Sep 18;7(1):11759 [PMID: 28924232]
  16. Neurochem Int. 2020 Nov;140:104840 [PMID: 32858090]
  17. J Neurol Neurosurg Psychiatry. 2019 May;90(5):590-598 [PMID: 30630955]
  18. Int J Mol Sci. 2022 Oct 27;23(21): [PMID: 36361780]
  19. IBRO Rep. 2019 Aug 01;7:59-69 [PMID: 31463415]
  20. Front Immunol. 2017 Mar 02;8:198 [PMID: 28303137]
  21. Redox Biol. 2022 Feb;49:102210 [PMID: 34922273]
  22. Antioxidants (Basel). 2021 Jun 01;10(6): [PMID: 34205998]
  23. Br J Pharmacol. 2017 Jun;174(12):1733-1749 [PMID: 26750203]
  24. Cells. 2024 Feb 04;13(3): [PMID: 38334675]
  25. J Clin Periodontol. 2018 Nov;45(11):1287-1298 [PMID: 30289998]
  26. Wien Klin Wochenschr. 2020 Sep;132(17-18):493-498 [PMID: 32215721]
  27. J Bacteriol. 2008 Apr;190(8):2920-32 [PMID: 18263730]
  28. Redox Biol. 2023 Dec;68:102955 [PMID: 37956598]
  29. J Alzheimers Dis. 2013;36(4):665-77 [PMID: 23666172]
  30. Front Cell Infect Microbiol. 2021 Mar 18;11:606986 [PMID: 33816329]
  31. Int J Mol Sci. 2018 Nov 30;19(12): [PMID: 30513656]
  32. Mol Neurobiol. 2019 Nov;56(11):7355-7367 [PMID: 31037648]
  33. Biochem Biophys Res Commun. 2020 Aug 27;529(3):747-752 [PMID: 32736702]
  34. Eur J Epidemiol. 2020 Sep;35(9):821-833 [PMID: 32533373]
  35. Physiol Rev. 2001 Apr;81(2):741-66 [PMID: 11274343]
  36. Antioxidants (Basel). 2020 Aug 13;9(8): [PMID: 32823544]
  37. Antioxid Redox Signal. 2022 Jan;36(1-3):15-38 [PMID: 34435888]
  38. BMC Microbiol. 2014 Jul 18;14:193 [PMID: 25037882]
  39. Int J Mol Sci. 2021 Jun 28;22(13): [PMID: 34203256]
  40. Nat Rev Immunol. 2021 Jul;21(7):426-440 [PMID: 33510490]
  41. Sci Rep. 2019 Feb 19;9(1):2296 [PMID: 30783129]
  42. Signal Transduct Target Ther. 2023 Sep 22;8(1):359 [PMID: 37735487]
  43. Eur J Immunol. 2014 Feb;44(2):328-38 [PMID: 24338806]
  44. Cold Spring Harb Perspect Med. 2012 Jan;2(1):a006346 [PMID: 22315714]

MeSH Term

Animals
Humans
Mice
Alzheimer Disease
Cell Line
Gene Expression Profiling
Host-Pathogen Interactions
Interleukin-6
Interleukin-8
Lipopolysaccharides
Microarray Analysis
Microglia
NADPH Oxidase 4
Neurons
Porphyromonas gingivalis
Reactive Oxygen Species

Chemicals

Interleukin-6
Interleukin-8
Lipopolysaccharides
NADPH Oxidase 4
NOX4 protein, human
Reactive Oxygen Species

Word Cloud

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