Journal Article

DZNE-2024-00071

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epileptic activity triggers rapid ROCK1-dependent astrocyte morphology changes.

Anders, S. ; Breithausen, B. ; Unichenko, P. ; Herde, M. K. ; Minge, D. ; Abramian, A. ; Behringer, C. ; Deshpande, T. ; Boehlen, A. ; Domingos, C. ; Henning, L. ; Pitsch, J. ; Kim, Y.-B. ; Bedner, P. ; Steinhäuser, C. ; Henneberger, C. (Last author)DZNE*

2024
Wiley-Liss Bognor Regis [u.a.]

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Please use a persistent id in citations: doi:10.1002/glia.24495

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.

Keyword(s): Humans (MeSH) ; Astrocytes (MeSH) ; rho-Associated Kinases (MeSH) ; Epilepsy (MeSH) ; Status Epilepticus (MeSH) ; Hippocampus (MeSH) ; ROCK signaling ; astrocytes ; epilepsy ; gap junction coupling ; morphology ; remodeling ; rho-Associated Kinases ; ROCK1 protein, human

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Contributing Institute(s):

1. Synaptic and Glial Plasticity (AG Henneberger)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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