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@ARTICLE{Blaschke:887855,
      author       = {Blaschke, Stefan J. and Demir, Seda and König, Anna and
                      Abraham, Jella-Andrea and Vay, Sabine U. and Rabenstein,
                      Monika and Olschewski, Daniel N. and Hoffmann, Christina and
                      Hoffmann, Marco and Hersch, Nils and Merkel, Rudolf and
                      Hoffmann, Bernd and Schroeter, Michael and Fink, Gereon R.
                      and Rueger, Maria A.},
      title        = {{S}ubstrate {E}lasticity {E}xerts {F}unctional {E}ffects on
                      {P}rimary {M}icroglia},
      journal      = {Frontiers in cellular neuroscience},
      volume       = {14},
      issn         = {1662-5102},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {FZJ-2020-04481},
      pages        = {590500},
      year         = {2020},
      abstract     = {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.},
      cin          = {INM-3 / IEK-9 / IBI-7 / IBI-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-3-20090406 / I:(DE-Juel1)IEK-9-20110218 /
                      I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)IBI-2-20200312},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33250714},
      UT           = {WOS:000591587300001},
      doi          = {10.3389/fncel.2020.590500},
      url          = {https://juser.fz-juelich.de/record/887855},
}