Department of Physiology, School of Medicine, University of Valencia, Spain.
Faculty of Surgery and Chiropody, University of Valencia, Spain.
J Alzheimers Dis. 2021;83(3):1051-1060. doi: 10.3233/JAD-210489.
In Alzheimer's disease (AD), an increase in inflammation is distinctive. Amyloid precursor protein plus presenilin-1 (APP/PS1 mice) is a model for this illness. Chemokines secreted by central nervous system (CNS) cells could play multiple important roles in AD. Data looking for the chemokines involved in inflammatory mechanisms are lacking. To understand the changes that occur in the inflammation process in AD, it is necessary to improve strategies to act on specific inflammatory targets.
Chemokines and their receptors involved in phagocytosis, demyelination, chemotaxis, and coagulation were the objective of our study.
Female APPswe/PS1 double-transgenic mice (B6C3-Tg) were used and cortex brain from 20-22-month-old mice obtained and used to quantify chemokines and chemokine receptors expression using RT-PCR technique.
Significant inflammatory changes were detected in APP/PS1 compared to wild type mice. CCR1, CCR3, CCR4, and CCR9 were elevated, and CCR2 were decreased compared with wild type mice. Their ligands CCL7, CCL11, CCL17, CCL22, CCL25, and CXCL4 showed an increase expression; however, changes were not observed in CCL2 in APP/PS1 compared to wild type mice.
This change in expression could explain the differences between AD patients and elderly people without this illness. This would provide a new strategy for the treatment of AD, with the possibility to act in specific inflammatory targets.
在阿尔茨海默病(AD)中,炎症增加是其特征。载脂蛋白前体蛋白加早老素-1(APP/PS1 小鼠)是这种疾病的模型。中枢神经系统(CNS)细胞分泌的趋化因子可能在 AD 中发挥多种重要作用。缺乏涉及炎症机制的趋化因子的数据。为了了解 AD 中炎症过程发生的变化,有必要改进针对特定炎症靶点的策略。
本研究的目的是研究参与吞噬作用、脱髓鞘、趋化和凝血的趋化因子及其受体。
使用雌性 APPswe/PS1 双转基因小鼠(B6C3-Tg),并获取 20-22 月龄小鼠的大脑皮质,使用 RT-PCR 技术定量分析趋化因子和趋化因子受体的表达。
与野生型小鼠相比,APP/PS1 中检测到明显的炎症变化。与野生型小鼠相比,CCR1、CCR3、CCR4 和 CCR9 升高,CCR2 降低。它们的配体 CCL7、CCL11、CCL17、CCL22、CCL25 和 CXCL4 的表达增加;然而,与野生型小鼠相比,APP/PS1 中 CCL2 的变化不明显。
这种表达的变化可以解释 AD 患者与没有这种疾病的老年人之间的差异。这将为 AD 的治疗提供一种新的策略,有可能针对特定的炎症靶点进行治疗。