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@ARTICLE{Anders:267062,
      author       = {Anders, Stefanie and Breithausen, Björn and Unichenko,
                      Petr and Herde, Michel K and Minge, Daniel and Abramian,
                      Adlin and Behringer, Charlotte and Deshpande, Tushar and
                      Boehlen, Anne and Domingos, Cátia and Henning, Lukas and
                      Pitsch, Julika and Kim, Young-Bum and Bedner, Peter and
                      Steinhäuser, Christian and Henneberger, Christian},
      title        = {{E}pileptic activity triggers rapid {ROCK}1-dependent
                      astrocyte morphology changes.},
      journal      = {Glia},
      volume       = {72},
      number       = {3},
      issn         = {0894-1491},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley-Liss},
      reportid     = {DZNE-2024-00071},
      pages        = {643 - 659},
      year         = {2024},
      abstract     = {Long-term modifications of astrocyte function and
                      morphology are well known to occur in epilepsy. They are
                      implicated in the development and manifestation of the
                      disease, but the relevant mechanisms and their
                      pathophysiological role are not firmly established. For
                      instance, it is unclear how quickly the onset of epileptic
                      activity triggers astrocyte morphology changes and what the
                      relevant molecular signals are. We therefore used two-photon
                      excitation fluorescence microscopy to monitor astrocyte
                      morphology in parallel to the induction of epileptiform
                      activity. We uncovered astrocyte morphology changes within
                      10-20 min under various experimental conditions in acute
                      hippocampal slices. In vivo, induction of status epilepticus
                      resulted in similarly altered astrocyte morphology within 30
                      min. Further analysis in vitro revealed a persistent volume
                      reduction of peripheral astrocyte processes triggered by
                      induction of epileptiform activity. In addition, an impaired
                      diffusion within astrocytes and within the astrocyte network
                      was observed, which most likely is a direct consequence of
                      the astrocyte remodeling. These astrocyte morphology changes
                      were prevented by inhibition of the Rho GTPase RhoA and of
                      the Rho-associated kinase (ROCK). Selective deletion of
                      ROCK1 but not ROCK2 from astrocytes also prevented the
                      morphology change after induction of epileptiform activity
                      and reduced epileptiform activity. Together these
                      observations reveal that epileptic activity triggers a rapid
                      ROCK1-dependent astrocyte morphology change, which is
                      mechanistically linked to the strength of epileptiform
                      activity. This suggests that astrocytic ROCK1 signaling is a
                      maladaptive response of astrocytes to the onset of epileptic
                      activity.},
      keywords     = {Humans / Astrocytes / rho-Associated Kinases / Epilepsy /
                      Status Epilepticus / Hippocampus / ROCK signaling (Other) /
                      astrocytes (Other) / epilepsy (Other) / gap junction
                      coupling (Other) / morphology (Other) / remodeling (Other) /
                      rho-Associated Kinases (NLM Chemicals) / ROCK1 protein,
                      human (NLM Chemicals)},
      cin          = {AG Henneberger},
      ddc          = {610},
      cid          = {I:(DE-2719)1013029},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10842783},
      pubmed       = {pmid:38031824},
      doi          = {10.1002/glia.24495},
      url          = {https://pub.dzne.de/record/267062},
}