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Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice

Authors :
Chairmandurai Aravindraja
Ravi Sakthivel
Xuefei Liu
Marshall Goodwin
Patnam Veena
Valentina Godovikova
J. Christopher Fenno
Yona Levites
Todd E. Golde
Lakshmyya Kesavalu
Source :
International Journal of Molecular Sciences; Volume 23; Issue 6; Pages: 3328
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

The impact of oral microbial dysbiosis on Alzheimer’s disease (AD) remains controversial. Building off recent studies reporting that various microbes might directly seed or promote amyloid β (Aβ) deposition, we evaluated the effects of periodontal bacteria (Porphyromonas gingivalis, Treponema denticola) and supragingival commensal (Streptococcus gordonii) oral bacterial infection in the APP-transgenic CRND8 (Tg) mice model of AD. We tracked bacterial colonization and dissemination, and monitored effects on gliosis and amyloid deposition. Chronic oral infection did not accelerate Aβ deposition in Tg mice but did induce alveolar bone resorption, IgG immune response, and an intracerebral astrogliosis (GFAP: glial fibrillary acidic protein). In contrast, intracerebral inoculation of live but not heat-killed P. gingivalis increased Aβ deposition and Iba-1 (ionized calcium-binding adaptor-1) microgliosis after 8 weeks of bacterial infection but not at 4 days. These data show that there may be differential effects of infectious microbes on glial activation and amyloid deposition depending on the species and route of inoculation, and thereby provide an important framework for future studies. Indeed, these studies demonstrate marked effects on amyloid β deposition only in a fairly non-physiologic setting where live bacteria is injected directly into the brain.

Details

Language :
English
ISSN :
14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 23; Issue 6; Pages: 3328
Accession number :
edsair.doi.dedup.....044ee155707a3290c2f6a3ce7f7d4489
Full Text :
https://doi.org/10.3390/ijms23063328