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目的 研究CD200R1对细菌脂多糖(lipopolysaccharide,LPS)诱导的小胶质细胞内吞功能的影响。方法 应用LPS激活小胶质细胞并通过荧光微球内吞实验观察小胶质细胞内吞水平的变化以及通过RT-qPCR检测CD200R1mRNA水平的表达,并在BV2-SH-SY5Y共培养模型中同样通过荧光微球内吞实验观察LPS诱导的小胶质细胞内吞功能的变化,最后利用CD200R1基因敲除小鼠提取原代培养的小胶质细胞并加LPS处理,通过荧光微球内吞实验观察其内吞功能的变化。结果 LPS激活小胶质细胞,促进了小胶质细胞内吞水平增加以及CD200R1表达下降。在BV2-SH-SY5Y共培养模型中,神经元细胞接触小胶质细胞后抑制LPS诱导的小胶质细胞内吞增加,CD200R1基因敲除的小胶质细胞加入LPS处理后,内吞水平增加更明显。结论 CD200R1基因敲除的小胶质细胞在LPS刺激后内吞水平增加更明显。 相似文献
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Margaret A Hamner Ashley McDonough Davin C Gong Levi J Todd German Rojas Sibylle Hodecker Christopher B Ransom Thomas A Reh Bruce R Ransom Jonathan RWeinstein 杜一星 《神经损伤与功能重建》2022,(2)
缺血预处理(ischemic preconditioning,IPC)是通过短暂、无害的缺血性暴露增强对随后发生的缺血障碍耐受性的现象。IPC的机制主要在灰质约占大脑85%的啮齿动物卒中模型中进行研究。人类脑白质占脑容量的50%,是卒中损伤的关键组成部分。我们使用小鼠视神经开发了一种新的中枢神经系统白质IPC模型,并确定了相关的免疫信号通路。我们验证了小胶质细胞对于白质IPC是必需的这一假说。首先用集落刺激因子1受体抑制剂PLX5622处理以耗尽小胶质细胞。视神经在体内暴露于短暂性缺血,72 h后急性分离,并进行氧-葡萄糖剥夺(OGD)以模拟缺血性损伤。通过记录复合动作电位(CAPs)和使用定量体视学的显微镜来评估轴突功能和结构的恢复。结果显示小胶质细胞耗竭消除了IPC介导的保护作用。在对照小鼠中,与非预处理视神经相比,预处理视神经的CAP恢复有所改善。然而在PLX5622处理的小鼠中,预处理和非预处理视神经之间的CAP恢复没有差异。小胶质细胞缺失还消除了IPC对OGD后轴突完整性和成熟(APC+)少突胶质细胞存活的保护作用。IPC介导的保护与视网膜损伤无关,表明它是由白质缺血暴露的固有的机械过程引起的。我们得出结论,预处理的小胶质细胞对白质中的IPC至关重要。"预处理的小胶质细胞"表型可能对其他中枢神经系统病变有保护作用,是值得探索的神经治疗领域。 相似文献
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目的:研究未活化和活化态人小胶质细胞系CHME-5培养上清液对鼻咽癌细胞CNE-2迁移、侵袭能力的影响。方法:采用1μg/mL LPS活化人小胶质细胞系CHME-5,收集未活化和LPS活化的CHME-5培养上清液。分为对照组(无血清培养基)、45%上清组、90%上清组、LPS组(LPS干预的小胶质细胞上清)、45%LPS上清组、90%LPS上清组。使用划痕实验和Transwell小室建立鼻咽癌细胞CNE-2的迁移模型,观察不同浓度的未活化/活化小胶质细胞培养上清液对鼻咽癌细胞迁移能力的影响;使用Transwell小室建立鼻咽癌细胞CNE-2的侵袭模型,用结晶紫染色观察不同浓度的未活化/活化小胶质细胞培养上清液对鼻咽癌细胞侵袭能力的影响。结果:低浓度(45%)和高浓度(90%)未活化/活化的小胶质细胞培养上清液均促进鼻咽癌细胞迁移和侵袭。结论:无论小胶质细胞是否活化,其培养上清液均促进鼻咽癌细胞的迁移和侵袭。 相似文献
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Elise C. Cope Maya Opendak Elizabeth A. LaMarca Sahana Murthy Christin Y. Park Lyra B. Olson Susana Martinez Jacqueline M. Leung Andrea L. Graham Elizabeth Gould 《Hippocampus》2019,29(4):366-377
The hippocampus of rodents undergoes structural remodeling throughout adulthood, including the addition of new neurons. Adult neurogenesis is sensitive to environmental enrichment and stress. Microglia, the brain's resident immune cells, are involved in adult neurogenesis by engulfing dying new neurons. While previous studies using laboratory environmental enrichment have investigated alterations in brain structure and function, they do not provide an adequate reflection of living in the wild, in which stress and environmental instability are common. Here, we compared mice living in standard laboratory settings to mice living in outdoor enclosures to assess the complex interactions among environment, gut infection, and hippocampal plasticity. We infected mice with parasitic worms and studied their effects on adult neurogenesis, microglia, and functions associated with the hippocampus, including cognition and anxiety regulation. We found an increase in immature neuron numbers of mice living in outdoor enclosures regardless of infection. While outdoor living prevented increases in microglial reactivity induced by infection in both the dorsal and ventral hippocampus, outdoor mice with infection had fewer microglia and microglial processes in the ventral hippocampus. We observed no differences in cognitive performance on the hippocampus‐dependent object location task between infected and uninfected mice living in either setting. However, we found that infection caused an increase in anxiety‐like behavior in the open field test but only in outdoor mice. These findings suggest that living conditions, as well as gut infection, interact to produce complex effects on brain structure and function. 相似文献
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Joana Mendes Duarte Rita Gaspar Liliana Caetano Patrícia Patrício Carina Soares-Cunha António Mateus-Pinheiro Nuno Dinis Alves Ana Rita Santos Samira G Ferreira Vanessa Sardinha João Filipe Oliveira Carlos Fontes-Ribeiro Nuno Sousa Rodrigo A. Cunha António F. Ambrósio Luísa Pinto Ana João Rodrigues Catarina A. Gomes 《Glia》2019,67(1):182-192
Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety-related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC-dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper-ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A2A receptors (A2AR), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety-like behavior. Notably, A2AR blockade rectified both microglia morphology in the dHIP and the lack of mPFC-dHIP synchronization, further heralding their role in cognitive function. 相似文献
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Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive‐like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll‐like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia‐neural communication, and the profound effects that glial‐derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region‐specific functions, and glia in different brain regions have distinct contributions to drug‐associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug‐induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction. 相似文献
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