TY  - JOUR
AU  - Anders, Stefanie
AU  - Breithausen, Björn
AU  - Unichenko, Petr
AU  - Herde, Michel K
AU  - Minge, Daniel
AU  - Abramian, Adlin
AU  - Behringer, Charlotte
AU  - Deshpande, Tushar
AU  - Boehlen, Anne
AU  - Domingos, Cátia
AU  - Henning, Lukas
AU  - Pitsch, Julika
AU  - Kim, Young-Bum
AU  - Bedner, Peter
AU  - Steinhäuser, Christian
AU  - Henneberger, Christian
TI  - Epileptic activity triggers rapid ROCK1-dependent astrocyte morphology changes.
JO  - Glia
VL  - 72
IS  - 3
SN  - 0894-1491
CY  - Bognor Regis [u.a.]
PB  - Wiley-Liss
M1  - DZNE-2024-00071
SP  - 643 - 659
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Astrocytes
KW  - rho-Associated Kinases
KW  - Epilepsy
KW  - Status Epilepticus
KW  - Hippocampus
KW  - ROCK signaling (Other)
KW  - astrocytes (Other)
KW  - epilepsy (Other)
KW  - gap junction coupling (Other)
KW  - morphology (Other)
KW  - remodeling (Other)
KW  - rho-Associated Kinases (NLM Chemicals)
KW  - ROCK1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10842783
C6  - pmid:38031824
DO  - DOI:10.1002/glia.24495
UR  - https://pub.dzne.de/record/267062
ER  -