Porphyromonas gingivalis (W83) Infection Induces Alzheimer’s Disease-Like Pathophysiology in Obese and Diabetic Mice

Bojlul Bahar, Shalini Kanagasingam, Murtaza M. Tambuwala, Alaa A.A. Aljabali, Stephanie A. Dillon, Saeid Doaei, Richard Welbury, Sasanka S. Chukkapalli, Sim K. Singhrao

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Abstract

Background: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. Objective: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer’s disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. Methods: The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. Results: While no Aβ plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aβ release in the same infection group. Conclusion: P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.
Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalJournal of Alzheimer's Disease
Volume82
Issue number3
DOIs
Publication statusPublished (in print/issue) - 3 Aug 2021

Bibliographical note

Funding Information:
SK and SKS in 2017 and again with BB and RW and SKS in 2018 received PreViser awards from the Oral and Dental Research Trust. In addition, SK also acknowledges having received a TC White Young Researcher award (2019). SC acknowledge the support from faculty seed grant (UFCD), University of Florida, Gainesville, FL, USA.

Publisher Copyright:
© 2021 - IOS Press. All rights reserved.

Keywords

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • General Medicine
  • inflammation
  • Therapeutics
  • Porphyromonas gingivalis
  • diabetes genes
  • Alzheimer's disease
  • insulin resistance

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