دورية أكاديمية

Substrate Elasticity Exerts Functional Effects on Primary Microglia

التفاصيل البيبلوغرافية
العنوان: Substrate Elasticity Exerts Functional Effects on Primary Microglia
المؤلفون: Blaschke, Stefan J., Demir, Seda, Merkel, Rudolf, Hoffmann, Bernd, Schroeter, Michael, Fink, Gereon R., Rueger, Maria A., König, Anna, Abraham, Jella-Andrea, Vay, Sabine U., Rabenstein, Monika, Olschewski, Daniel N., Hoffmann, Christina, Hoffmann, Marco, Hersch, Nils
المصدر: Frontiers in cellular neuroscience 14, 590500 (2020). doi:10.3389/fncel.2020.590500
بيانات النشر: Frontiers Research Foundation
سنة النشر: 2020
المجموعة: Forschungszentrum Jülich: JuSER (Juelich Shared Electronic Resources)
مصطلحات موضوعية: info:eu-repo/classification/ddc/610
جغرافية الموضوع: DE
الوصف: 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 ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/pmid:33250714; info:eu-repo/semantics/altIdentifier/hdl/2128/26153; info:eu-repo/semantics/altIdentifier/issn/1662-5102; info:eu-repo/semantics/altIdentifier/wos/WOS:000591587300001; https://juser.fz-juelich.de/record/887855Test; https://juser.fz-juelich.de/search?p=id:%22FZJ-2020-04481%22Test
الإتاحة: https://doi.org/10.3389/fncel.2020.590500Test
https://juser.fz-juelich.de/record/887855Test
https://juser.fz-juelich.de/search?p=id:%22FZJ-2020-04481%22Test
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.FB196F82
قاعدة البيانات: BASE