Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Brain Research Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC V6T 2B5, Canada.
Neuron. 2014 Apr 2;82(1):195-207. doi: 10.1016/j.neuron.2014.01.043. Epub 2014 Mar 13.
Complement receptor 3 (CR3) activation in microglia is involved in neuroinflammation-related brain disorders and pruning of neuronal synapses. Hypoxia, often observed together with neuroinflammation in brain trauma, stroke, and neurodegenerative diseases, is thought to exacerbate inflammatory responses and synergistically enhance brain damage. Here we show that when hypoxia and an inflammatory stimulus (lipopolysaccharide [LPS]) are combined, they act synergistically to trigger long-term synaptic depression (LTD) that requires microglial CR3, activation of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and GluA2-mediated A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Microglial CR3-triggered LTD is independent of N-methyl-D-aspartate receptors (NMDARs), metabotropic glutamate receptors (mGluRs), or patterned synaptic activity. This type of LTD may contribute to memory impairments and synaptic disruptions in neuroinflammation-related brain disorders.
补体受体 3（CR3）在小胶质细胞中的激活与神经炎症相关的脑疾病和神经元突触修剪有关。缺氧常与脑外伤、中风和神经退行性疾病中的神经炎症同时发生，被认为会加剧炎症反应并协同增强脑损伤。在这里，我们表明，当缺氧和炎症刺激（脂多糖[LPS]）结合时，它们会协同作用触发需要小胶质细胞 CR3、烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH 氧化酶）激活和 GluA2 介导的 A-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）内化的长时程突触抑制（LTD）。小胶质细胞 CR3 触发的 LTD 与 N-甲基-D-天冬氨酸受体（NMDARs）、代谢型谷氨酸受体（mGluRs）或模式化突触活动无关。这种类型的 LTD 可能导致神经炎症相关脑疾病中的记忆障碍和突触破坏。
