阿尔茨海默病小胶质细胞CX3CR1产物增加并受去甲肾上腺素的调节  

Microglial CX3CR1 production increases in Alzheimer's disease and is regulated by noradrenaline

作　　者：Marta González-Prieto Irene LGutiérrez Borja García-Bueno Javier RCaso Juan CLeza Adriana Ortega-Hernández Dulcenombre Gómez-Garre JoséLMMadrigal 杜一星(编译) 

机构地区：[1]Department of Pharmacology and Toxicology,School of Medicine,Universidad Complutense de Madrid(UCM),Madrid,Spain [2]Centro de Investigación Biomédica en Red de Salud Mental(CIBERSAM),Instituto de Investigación Neuroquímica(IUINQ-UCM),Instituto de Investigación Sanitaria Hospital,Madrid,Spain [3]Vascular Biology Laboratory and Flow Cytometric Unit,Hospital Clínico San Carlos-Instituto de Investigación Sanitaria San Carlos(IdISSC),Madrid,Spain [4]Biomedical Research Networking Center in Cardiovascular Diseases(CIBERCV),Madrid,Spain [5]不详

出　　处：《神经损伤与功能重建》2020年第7期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：去甲肾上腺素能神经元的丧失及其引起的脑去甲肾上腺素(NA)水平的降低与阿尔茨海默病(AD)的进展有关。这似乎主要是由于NA减少小胶质细胞活化的能力。我们以前观察到NA诱导神经元产生趋化因子Fractalkine/CX3CL1。小胶质细胞CX3CR1(CX3CL1的唯一受体)的激活会减少小胶质细胞的活化,已知这在很大程度上引起AD特征性的神经元损伤。因此,操控小胶质细胞中CX3CR1的产物可能转化为对CX3CL1抗炎作用的增强或抑制。为了确定小胶质细胞CX3CR1产物在AD中是否发生改变,以及NA是否可以控制这种改变,我们在5xFAD小鼠和人类AD脑样本中分析了CX3CR1的表达和合成。此外,我们分别在小胶质细胞培养物和小鼠中分析了NA及NA再摄取抑制剂瑞波西汀的作用。我们的结果表明,CX3CR1在AD大脑皮质中的产量增加,而给予瑞波西汀进一步增加了它的含量,并增强了小胶质对淀粉样β斑的反应性。然而,直接向原代大鼠小胶质细胞或人类HMC3细胞给予NA会抑制CX3CR1的产生,这表明小胶质细胞对NA的反应可能会在不存在产生CX3CL1的神经元或其他非小胶质外在因素的作用下发生改变。The loss of noradrenergic neurons and subsequent reduction of brain noradrenaline(NA)levels are associated with the progression of Alzheimer's disease(AD).This seems to be due mainly to the ability of NA to reduce the activation of microglial cells.We previously observed that NA induces the production of the chemokine Fractalkine/CX3CL1 in neurons.The activation of microglial CX3CR1,sole receptor for CX3CL1,reduces the activation of microglia,which is known to largely contribute to the neuronal damage characteristic of AD.Therefore,alterations of CX3CR1 production in microglia could translate into the enhancement or inhibition of CX3CL1 anti‐inflammatory effects.In order to determine if microglial CX3CR1 production is altered in AD and if NA can control it,CX3CR1 expression and synthesis were analyzed in 5xFAD mice and human AD brain samples.In addition,the effects of NA and its reuptake inhibitor reboxetine were analyzed in microglial cultures and mice respectively.Our results indicate that in AD CX3CR1 production is increased in the brain cortex and that reboxetine administration further increases it and enhances microglial reactivity toward amyloid beta plaques.However,direct administration of NA to primary rat microglia or human HMC3 cells inhibits CX3CR1 production,suggesting that microglia responses to NA may be altered in the absence of CX3CL1‐producing neurons or other nonmicroglial external factors.

关 键 词：(5-7)CX3C趋化因子受体1 表达5种人类AβPP和PS1突变的小鼠 阿尔茨海默病 C-X3-C基序趋化因子配体1 不规则趋化因子 去甲肾上腺素 瑞波西汀 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]