Substrate Elasticity Exerts Functional Effects on Primary Microglia.
Substrate Elasticity Exerts Functional Effects on Primary Microglia.
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DOI：
10.3389/fncel.2020.590500
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发表时间：
2020
影响因子：
5.3
通讯作者：
Rueger MA
中科院分区：
文献类型：
--
作者：
Blaschke SJ;Demir S;König A;Abraham JA;Vay SU;Rabenstein M;Olschewski DN;Hoffmann C;Hoffmann M;Hersch N;Merkel R;Hoffmann B;Schroeter M;Fink GR;Rueger MA
小胶质细胞--大脑的主要免疫细胞--在大脑病理学中发挥严格调节的促炎和抗炎作用，促进再生或神经变性。因此，利用小胶质细胞成为神经学研究中一个潜在的治疗概念。最近的研究表明，除了受到趋化因子和细胞因子的影响，大脑中的各种细胞实体对其微环境的机械特性做出相关反应。例如，我们最近报道了弹性对神经干细胞的静止和分化潜力的显著影响。然而，弹性对小胶质细胞的影响仍有待探讨，在假设的微环境的弹性影响的关键特性和功能的小胶质细胞，我们建立了原代大鼠小胶质细胞在聚二甲基硅氧烷（PDMS）的细胞培养系统的体外模型。通过这种方式，我们模拟了大脑的生理弹性范围，并将其与超生理刚性PDMS对照进行了比较。我们评估了小胶质细胞在“静息”条件下的功能参数，以及当通过脂多糖（LPS）向促炎表型（M1）极化或通过白细胞介素-4（IL-4）向抗炎表型（M2）极化时的功能参数。小胶质细胞的活力是未受损的软基板上，但我们发现了各种显着的影响，超过2倍的小胶质细胞增殖的软基板弹性模仿大脑（相对于PDMS控制）。此外，软基板促进小胶质细胞中的活化标志物波形蛋白的表达。此外，M2标记物CD 206上调平行于胰岛素样生长因子-1（IGF-1）分泌的增加。阻断牵张依赖性氯离子通道可消除CD 206的上调。我们的数据表明，在类脑弹性基质上培养小胶质细胞通过牵张依赖性氯离子通道促进基本抗炎激活状态。这些结果突出了对小胶质细胞施加的无所不在但大多被忽视的机械生物学效应的重要性，并有助于更好地理解小胶质细胞，神经干细胞和胶质细胞在健康和疾病中复杂的空间和时间相互作用。
Microglia—the brain’s primary immune cells—exert a tightly regulated cascade of pro- and anti-inflammatory effects upon brain pathology, either promoting regeneration or neurodegeneration. Therefore, harnessing microglia emerges as a potential therapeutic concept in neurological research. Recent studies suggest that—besides being affected by chemokines and cytokines—various cell entities in the brain relevantly respond to the mechanical properties of their microenvironment. For example, we lately reported considerable effects of elasticity on neural stem cells, regarding quiescence and differentiation potential. However, the effects of elasticity on microglia remain to be explored.Under the hypothesis that the elasticity of the microenvironment affects key characteristics and functions of microglia, we established an in vitro model of primary rat microglia grown in a polydimethylsiloxane (PDMS) elastomer-based cell culture system. This way, we simulated the brain’s physiological elasticity range and compared it to supraphysiological stiffer PDMS controls. We assessed functional parameters of microglia under “resting” conditions, as well as when polarized towards a pro-inflammatory phenotype (M1) by lipopolysaccharide (LPS), or an anti-inflammatory phenotype (M2) by interleukin-4 (IL-4). Microglia viability was unimpaired on soft substrates, but we found various significant effects with a more than two-fold increase in microglia proliferation on soft substrate elasticities mimicking the brain (relative to PDMS controls). Furthermore, soft substrates promoted the expression of the activation marker vimentin in microglia. Moreover, the M2-marker CD206 was upregulated in parallel to an increase in the secretion of Insulin-Like Growth Factor-1 (IGF-1). The upregulation of CD206 was abolished by blockage of stretch-dependent chloride channels. Our data suggest that the cultivation of microglia on substrates of brain-like elasticity promotes a basic anti-inflammatory activation state via stretch-dependent chloride channels. The results highlight the significance of the omnipresent but mostly overlooked mechanobiological effects exerted on microglia and contribute to a better understanding of the complex spatial and temporal interactions between microglia, neural stem cells, and glia, in health and disease.
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通过磁共振弹性成像确定阿尔茨海默氏病的大脑硬度降低。
影响因子：
4.4
作者：
Murphy, Matthew C.;Huston, John, III;Jack, Clifford R., Jr.;Glaser, Kevin J.;Manduca, Armando;Felmlee, Joel P.;Ehman, Richard L.
通讯作者：
Ehman, Richard L.
影响因子：
5.7
作者：
Murphy MC;Huston J 3rd;Ehman RL
通讯作者：
Ehman RL
影响因子：
5.5
作者：
Kim JY;Kim N;Yenari MA
通讯作者：
Yenari MA
影响因子：
4.2
作者：
Hiscox LV;Johnson CL;McGarry MDJ;Perrins M;Littlejohn A;van Beek EJR;Roberts N;Starr JM
通讯作者：
Starr JM
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW