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

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 dentic...

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Autores principales: Aravindraja, Chairmandurai, Sakthivel, Ravi, Liu, Xuefei, Goodwin, Marshall, Veena, Patnam, Godovikova, Valentina, Fenno, J. Christopher, Levites, Yona, Golde, Todd E., Kesavalu, Lakshmyya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954230/
https://www.ncbi.nlm.nih.gov/pubmed/35328748
http://dx.doi.org/10.3390/ijms23063328
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author Aravindraja, Chairmandurai
Sakthivel, Ravi
Liu, Xuefei
Goodwin, Marshall
Veena, Patnam
Godovikova, Valentina
Fenno, J. Christopher
Levites, Yona
Golde, Todd E.
Kesavalu, Lakshmyya
author_facet Aravindraja, Chairmandurai
Sakthivel, Ravi
Liu, Xuefei
Goodwin, Marshall
Veena, Patnam
Godovikova, Valentina
Fenno, J. Christopher
Levites, Yona
Golde, Todd E.
Kesavalu, Lakshmyya
author_sort Aravindraja, Chairmandurai
collection PubMed
description 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.
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spelling pubmed-89542302022-03-26 Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice Aravindraja, Chairmandurai Sakthivel, Ravi Liu, Xuefei Goodwin, Marshall Veena, Patnam Godovikova, Valentina Fenno, J. Christopher Levites, Yona Golde, Todd E. Kesavalu, Lakshmyya Int J Mol Sci Article 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. MDPI 2022-03-19 /pmc/articles/PMC8954230/ /pubmed/35328748 http://dx.doi.org/10.3390/ijms23063328 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aravindraja, Chairmandurai
Sakthivel, Ravi
Liu, Xuefei
Goodwin, Marshall
Veena, Patnam
Godovikova, Valentina
Fenno, J. Christopher
Levites, Yona
Golde, Todd E.
Kesavalu, Lakshmyya
Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title_full Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title_fullStr Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title_full_unstemmed Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title_short Intracerebral but Not Peripheral Infection of Live Porphyromonas gingivalis Exacerbates Alzheimer’s Disease Like Amyloid Pathology in APP-TgCRND8 Mice
title_sort intracerebral but not peripheral infection of live porphyromonas gingivalis exacerbates alzheimer’s disease like amyloid pathology in app-tgcrnd8 mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954230/
https://www.ncbi.nlm.nih.gov/pubmed/35328748
http://dx.doi.org/10.3390/ijms23063328
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