年龄和性别相关的牙周骨吸收、认知功能和免疫状态在阿尔茨海默病 APP/PS1 小鼠模型中的差异。
Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP/PS1 murine model of Alzheimer's disease.
机构信息
Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
出版信息
J Neuroinflammation. 2023 Jun 27;20(1):153. doi: 10.1186/s12974-023-02790-1.
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.
背景
越来越多的证据证实，认知障碍与牙周炎之间存在相互关联的机制。然而，这种机制中年龄或性别差异的作用研究较少。本研究旨在探讨 APP/PS1 阿尔茨海默病（AD）小鼠模型中牙周骨组织、免疫状态和认知功能的性别和年龄差异。
方法
本研究使用了 3 个月和 12 个月龄的雄性和雌性 APP/PS1 转基因小鼠和野生型（WT）同窝仔鼠。使用 Morris 水迷宫（MWM）评估认知功能。通过微计算机断层扫描（micro-CT）评估后上颌牙槽骨的骨微结构。通过组织化学观察牙周骨组织的病理变化。通过流式细胞术评估外周血单个核细胞（PBMCs）和脑组织中辅助性 T 细胞 1（Th1）、Th2、Th17 和调节性 T 细胞（Tregs）的比例。
结果
12 月龄 APP/PS1 小鼠的学习能力和空间记忆严重受损。认知功能的变化仅与年龄和基因型相关，而与性别无关。12 月龄 APP/PS1 雌性小鼠表现出明显的牙周骨退化，表现为骨体积/总体积（BV/TV）、骨小梁厚度（Tb.Th）和骨密度（BMD）降低，而骨小梁分离度（Tb.Sp）增加。改变的牙周骨微结构与基因型、年龄和性别有关。与年龄和性别匹配的 WT 小鼠相比，12 月龄 APP/PS1 小鼠的大脑和 PBMC 样本中 Th1 和 Th17 细胞增加，Th2 细胞减少。然而，年龄或性别与这种免疫状态之间没有统计学相关性。
结论
我们的数据强调，在评估 APP/PS1 小鼠的牙周骨组织时，年龄和性别是重要的考虑因素，认知障碍与年龄更相关。此外，在 APP/PS1 小鼠的脑组织和 PBMC 中发现了免疫失调（Th1、Th2 和 Th17 细胞），但这种免疫状态的改变与性别或年龄没有统计学相关性。
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