Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents.
Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents.
复制标题
与年龄相关的炎症平衡转移，鼻屏障功能以及健康和患病啮齿动物的脑形象状态。
DOI：
10.3389/fnins.2021.700729
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发表时间：
2021
影响因子：
4.3
通讯作者：
Erdő F
中科院分区：
文献类型：
--
作者：
Varga-Medveczky Z;Kovács N;Tóth ME;Sántha M;Horváth I;Bors LA;Fónagy K;Imre T;Szabó P;Máthé D;Erdő F
早些时候，在健康和病理性衰老的小鼠模型中，已经描述了血脑屏障(BBB)通透性的增加和广泛的神经元变化，如载脂蛋白B-100(APOB-100)和淀粉样前体蛋白(APP)-早老素-1(PSEN1)转基因小鼠模型。ApoB-100高甘油三酯血症模型是研究脑血管病变与神经退行性变之间联系的有用工具，而APP-PSEN1人源化小鼠是阿尔茨海默病的模型。目前这项研究的目的是描述健康衰老和神经退行性变中大脑的炎性变化。此外，还对脑形态和认知的改变进行了研究。在疾病模型中监测P-糖蛋白底物模型药物奎尼丁的鼻脑给药情况，并与年龄匹配的对照组进行比较。我们的结果显示，在健康的老年人和神经退行性变的模型中，炎症平衡都发生了变化。在正常衰老中，单核细胞趋化蛋白-1、干细胞因子和RANTES高度上调，表明白细胞处于刺激状态。在APOB-100小鼠中，血管内皮生长因子(VEGF)、血小板衍生生长因子(PDGF-BB)和白介素17A(IL-17A)被诱导(血管反应)，而在APP-PSEN1小鼠中，抵抗素、IL-17A和GM-CSF主要被上调。鼻腔药物在脑和血液中的吸收相似，表明血脑屏障的分子旁路。学习和记忆测试表明，健康的老年和幼年动物的认知表现没有差异。根据这些结果，可以得出结论，在健康、老年和患病的动物中存在各种慢性炎症标记物。在APOB-100小鼠身上，也可以观察到脑室扩张。为了开发合适的抗衰老和神经保护化合物，建议对上述炎症靶点进行进一步研究。
Increased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic model is a useful tool to study the link between cerebrovascular pathology and neurodegeneration, while APP–PSEN1 humanized mouse is a model of Alzheimer’s disease. The aim of the current study was to characterize the inflammatory changes in the brain with healthy aging and in neurodegeneration. Also, the cerebro-morphological and cognitive alterations have been investigated. The nose-to-brain delivery of a P-glycoprotein substrate model drug (quinidine) was monitored in the disease models and compared with the age-matched controls. Our results revealed an inflammatory balance shift in both the healthy aged and neurodegenerative models. In normal aging monocyte chemoattractant protein-1, stem cell factor and Rantes were highly upregulated indicating a stimulated leukocyte status. In APOB-100 mice, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), and interleukin-17A (IL-17A) were induced (vascular reaction), while in APP–PSEN1 mice resistin, IL-17A and GM-CSF were mostly upregulated. The nasal drug absorption was similar in the brain and blood indicating the molecular bypass of the BBB. The learning and memory tests showed no difference in the cognitive performance of healthy aged and young animals. Based on these results, it can be concluded that various markers of chronic inflammation are present in healthy aged and diseased animals. In APOB-100 mice, a cerebro-ventricular dilation can also be observed. For development of proper anti-aging and neuroprotective compounds, further studies focusing on the above inflammatory targets are suggested.
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影响因子：
5.3
作者：
Hoyk Z;Tóth ME;Lénárt N;Nagy D;Dukay B;Csefová A;Zvara Á;Seprényi G;Kincses A;Walter FR;Veszelka S;Vígh J;Barabási B;Harazin A;Kittel Á;Puskás LG;Penke B;Vígh L;Deli MA;Sántha M
通讯作者：
Sántha M
影响因子：
2.1
作者：
Baba T;Mukaida N
通讯作者：
Mukaida N
影响因子：
64.8
作者：
HIRANO, T;YASUKAWA, K;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
3.6
作者：
Harrison, F. E.;Hosseini, A. H.;May, J. M.
通讯作者：
May, J. M.
影响因子：
4
作者：
Badoer E;Kosari S;Stebbing MJ
通讯作者：
Stebbing MJ