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Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease

BACKGROUND: The existence of an interconnected mechanism between cognitive disorders and periodontitis has been confirmed by mounting evidence. However, the role of age or sex differences in this mechanism has been less studied. This study aims to investigate sex and age differences in the character...

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Autores principales: Chen, Huiwen, Liao, Yue, Zhang, Xu, Shen, Hui, Shang, Dihua, He, Zhiyan, Zhou, Wei, Song, Zhongchen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294321/
https://www.ncbi.nlm.nih.gov/pubmed/37370108
http://dx.doi.org/10.1186/s12974-023-02790-1
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author Chen, Huiwen
Liao, Yue
Zhang, Xu
Shen, Hui
Shang, Dihua
He, Zhiyan
Zhou, Wei
Song, Zhongchen
author_facet Chen, Huiwen
Liao, Yue
Zhang, Xu
Shen, Hui
Shang, Dihua
He, Zhiyan
Zhou, Wei
Song, Zhongchen
author_sort Chen, Huiwen
collection PubMed
description BACKGROUND: The existence of an interconnected mechanism between cognitive disorders and periodontitis has been confirmed by mounting evidence. However, the role of age or sex differences in this mechanism has been less studied. This study aims to investigate sex and age differences in the characterization of periodontal bone tissue, immune state and cognitive function in amyloid precursor protein/presenilin 1(APP/PS1) murine model of Alzheimer’s disease (AD). METHODS: Three- and twelve-month-old male and female APP/PS1 transgenic mice and wild-type (WT) littermates were used in this study. The Morris water maze (MWM) was used to assess cognitive function. The bone microarchitecture of the posterior maxillary alveolar bone was evaluated by microcomputed tomography (micro-CT). Pathological changes in periodontal bone tissue were observed by histological chemistry. The proportions of helper T cells1 (Th1), Th2, Th17 and regulatory T cells (Tregs) in the peripheral blood mononuclear cells (PBMCs) and brain samples were assessed by flow cytometry. RESULTS: The learning ability and spatial memory of 12-month-old APP/PS1 mice was severely damaged. The changes in cognitive function were only correlated with age and genotype, regardless of sex. The 12-month-old APP/PS1 female mice exhibited markedly periodontal bone degeneration, evidenced by the decreased bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and bone mineral density (BMD), and the increased trabecular separation (Tb.Sp). The altered periodontal bone microarchitecture was associated with genotype, age and females. The flow cytometry data showed the increased Th1 and Th17 cells and the decreased Th2 cells in the brain and PBMC samples of 12-month-old APP/PS1 mice, compared to age- and sex-matched WT mice. However, there was no statistical correlation between age or sex and this immune state. CONCLUSIONS: Our data emphasize that age and sex are important variables to consider in evaluating periodontal bone tissue of APP/PS1 mice, and the cognitive impairment is more related to age. In addition, immune dysregulation (Th1, Th2, and Th17 cells) was found in the brain tissue and PBMCs of APP/PS1 mice, but this alteration of immune state was not statistically correlated with sex or age. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02790-1.
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spelling pubmed-102943212023-06-28 Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease Chen, Huiwen Liao, Yue Zhang, Xu Shen, Hui Shang, Dihua He, Zhiyan Zhou, Wei Song, Zhongchen J Neuroinflammation Original Paper BACKGROUND: The existence of an interconnected mechanism between cognitive disorders and periodontitis has been confirmed by mounting evidence. However, the role of age or sex differences in this mechanism has been less studied. This study aims to investigate sex and age differences in the characterization of periodontal bone tissue, immune state and cognitive function in amyloid precursor protein/presenilin 1(APP/PS1) murine model of Alzheimer’s disease (AD). METHODS: Three- and twelve-month-old male and female APP/PS1 transgenic mice and wild-type (WT) littermates were used in this study. The Morris water maze (MWM) was used to assess cognitive function. The bone microarchitecture of the posterior maxillary alveolar bone was evaluated by microcomputed tomography (micro-CT). Pathological changes in periodontal bone tissue were observed by histological chemistry. The proportions of helper T cells1 (Th1), Th2, Th17 and regulatory T cells (Tregs) in the peripheral blood mononuclear cells (PBMCs) and brain samples were assessed by flow cytometry. RESULTS: The learning ability and spatial memory of 12-month-old APP/PS1 mice was severely damaged. The changes in cognitive function were only correlated with age and genotype, regardless of sex. The 12-month-old APP/PS1 female mice exhibited markedly periodontal bone degeneration, evidenced by the decreased bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and bone mineral density (BMD), and the increased trabecular separation (Tb.Sp). The altered periodontal bone microarchitecture was associated with genotype, age and females. The flow cytometry data showed the increased Th1 and Th17 cells and the decreased Th2 cells in the brain and PBMC samples of 12-month-old APP/PS1 mice, compared to age- and sex-matched WT mice. However, there was no statistical correlation between age or sex and this immune state. CONCLUSIONS: Our data emphasize that age and sex are important variables to consider in evaluating periodontal bone tissue of APP/PS1 mice, and the cognitive impairment is more related to age. In addition, immune dysregulation (Th1, Th2, and Th17 cells) was found in the brain tissue and PBMCs of APP/PS1 mice, but this alteration of immune state was not statistically correlated with sex or age. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02790-1. BioMed Central 2023-06-27 /pmc/articles/PMC10294321/ /pubmed/37370108 http://dx.doi.org/10.1186/s12974-023-02790-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Original Paper
Chen, Huiwen
Liao, Yue
Zhang, Xu
Shen, Hui
Shang, Dihua
He, Zhiyan
Zhou, Wei
Song, Zhongchen
Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title_full Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title_fullStr Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title_full_unstemmed Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title_short Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer’s disease
title_sort age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in app/ps1 murine model of alzheimer’s disease
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10294321/
https://www.ncbi.nlm.nih.gov/pubmed/37370108
http://dx.doi.org/10.1186/s12974-023-02790-1
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