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000267062 1001_ $$aAnders, Stefanie$$b0
000267062 245__ $$aEpileptic activity triggers rapid ROCK1-dependent astrocyte morphology changes.
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000267062 520__ $$aLong-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.
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000267062 650_7 $$2Other$$aROCK signaling
000267062 650_7 $$2Other$$aastrocytes
000267062 650_7 $$2Other$$aepilepsy
000267062 650_7 $$2Other$$agap junction coupling
000267062 650_7 $$2Other$$amorphology
000267062 650_7 $$2Other$$aremodeling
000267062 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$arho-Associated Kinases
000267062 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aROCK1 protein, human
000267062 650_2 $$2MeSH$$aHumans
000267062 650_2 $$2MeSH$$aAstrocytes
000267062 650_2 $$2MeSH$$arho-Associated Kinases
000267062 650_2 $$2MeSH$$aEpilepsy
000267062 650_2 $$2MeSH$$aStatus Epilepticus
000267062 650_2 $$2MeSH$$aHippocampus
000267062 7001_ $$aBreithausen, Björn$$b1
000267062 7001_ $$aUnichenko, Petr$$b2
000267062 7001_ $$aHerde, Michel K$$b3
000267062 7001_ $$aMinge, Daniel$$b4
000267062 7001_ $$aAbramian, Adlin$$b5
000267062 7001_ $$aBehringer, Charlotte$$b6
000267062 7001_ $$aDeshpande, Tushar$$b7
000267062 7001_ $$aBoehlen, Anne$$b8
000267062 7001_ $$aDomingos, Cátia$$b9
000267062 7001_ $$aHenning, Lukas$$b10
000267062 7001_ $$aPitsch, Julika$$b11
000267062 7001_ $$aKim, Young-Bum$$b12
000267062 7001_ $$00000-0003-0090-7553$$aBedner, Peter$$b13
000267062 7001_ $$00000-0003-2579-8357$$aSteinhäuser, Christian$$b14
000267062 7001_ $$0P:(DE-2719)2811625$$aHenneberger, Christian$$b15$$eLast author$$udzne
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