CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression
PurposeEpilepsy therapy is currently based on anti-seizure drugs that do not modify the course of the disease, i.e., they are not anti-epileptogenic in nature. Previously, we observed that in vivo casein kinase 2 (CK2) inhibition with 4,5,6,7-tetrabromotriazole (TBB) had anti-epileptogenic effects i...
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doaj-a549a4bd1146428f822827468387da252020-11-25T03:00:53ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-02-011410.3389/fncel.2020.00033490483CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease ProgressionFelix Schulze0Steffen Müller1Xiati Guli2Lukas Schumann3Hannes Brehme4Till Riffert5Marco Rohde6Doreen Goerss7Doreen Goerss8Simone Rackow9Anne Einsle10Timo Kirschstein11Timo Kirschstein12Rüdiger Köhling13Rüdiger Köhling14Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyDepartment of Psychosomatic Medicine, Rostock University Medical Center, Rostock, GermanyGerman Center for Neurodegenerative Diseases (DZNE), Göttingen, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyCenter of Transdisciplinary Neurosciences Rostock, University of Rostock, Rostock, GermanyOscar Langendorff Institute of Physiology, University of Rostock, Rostock, GermanyCenter of Transdisciplinary Neurosciences Rostock, University of Rostock, Rostock, GermanyPurposeEpilepsy therapy is currently based on anti-seizure drugs that do not modify the course of the disease, i.e., they are not anti-epileptogenic in nature. Previously, we observed that in vivo casein kinase 2 (CK2) inhibition with 4,5,6,7-tetrabromotriazole (TBB) had anti-epileptogenic effects in the acute epilepsy slice model.MethodsHere, we pretreated rats with TBB in vivo prior to the establishment of a pilocarpine-induced status epilepticus (SE) in order to analyze the long-term sequelae of such a preventive TBB administration.ResultsWe found that TBB pretreatment delayed onset of seizures after pilocarpine and slowed down disease progression during epileptogenesis. This was accompanied with a reduced proportion of burst firing neurons in the CA1 area. Western blot analyses demonstrated that CA1 tissue from TBB-pretreated epileptic animals contained significantly less CK2 than TBB-pretreated controls. On the transcriptional level, TBB pretreatment led to differential gene expression changes of KCa2.2, but also of HCN1 and HCN3 channels. Thus, in the presence of the HCN channel blocker ZD7288, pretreatment with TBB rescued the afterhyperpolarizing potential (AHP) as well as spike frequency adaptation in epileptic animals, both of which are prominent functions of KCa2 channels.ConclusionThese data indicate that TBB pretreatment prior to SE slows down disease progression during epileptogenesis involving increased KCa2 function, probably due to a persistently decreased CK2 protein expression.https://www.frontiersin.org/article/10.3389/fncel.2020.00033/fulltemporal lobe epilepsypatch-clampintracellular recordingfield potential recordingvideo-EEG monitoringTimm stain |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Felix Schulze Steffen Müller Xiati Guli Lukas Schumann Hannes Brehme Till Riffert Marco Rohde Doreen Goerss Doreen Goerss Simone Rackow Anne Einsle Timo Kirschstein Timo Kirschstein Rüdiger Köhling Rüdiger Köhling |
spellingShingle |
Felix Schulze Steffen Müller Xiati Guli Lukas Schumann Hannes Brehme Till Riffert Marco Rohde Doreen Goerss Doreen Goerss Simone Rackow Anne Einsle Timo Kirschstein Timo Kirschstein Rüdiger Köhling Rüdiger Köhling CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression Frontiers in Cellular Neuroscience temporal lobe epilepsy patch-clamp intracellular recording field potential recording video-EEG monitoring Timm stain |
author_facet |
Felix Schulze Steffen Müller Xiati Guli Lukas Schumann Hannes Brehme Till Riffert Marco Rohde Doreen Goerss Doreen Goerss Simone Rackow Anne Einsle Timo Kirschstein Timo Kirschstein Rüdiger Köhling Rüdiger Köhling |
author_sort |
Felix Schulze |
title |
CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression |
title_short |
CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression |
title_full |
CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression |
title_fullStr |
CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression |
title_full_unstemmed |
CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KCa2 Function in CA1 Which Slows Down Disease Progression |
title_sort |
ck2 inhibition prior to status epilepticus persistently enhances kca2 function in ca1 which slows down disease progression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2020-02-01 |
description |
PurposeEpilepsy therapy is currently based on anti-seizure drugs that do not modify the course of the disease, i.e., they are not anti-epileptogenic in nature. Previously, we observed that in vivo casein kinase 2 (CK2) inhibition with 4,5,6,7-tetrabromotriazole (TBB) had anti-epileptogenic effects in the acute epilepsy slice model.MethodsHere, we pretreated rats with TBB in vivo prior to the establishment of a pilocarpine-induced status epilepticus (SE) in order to analyze the long-term sequelae of such a preventive TBB administration.ResultsWe found that TBB pretreatment delayed onset of seizures after pilocarpine and slowed down disease progression during epileptogenesis. This was accompanied with a reduced proportion of burst firing neurons in the CA1 area. Western blot analyses demonstrated that CA1 tissue from TBB-pretreated epileptic animals contained significantly less CK2 than TBB-pretreated controls. On the transcriptional level, TBB pretreatment led to differential gene expression changes of KCa2.2, but also of HCN1 and HCN3 channels. Thus, in the presence of the HCN channel blocker ZD7288, pretreatment with TBB rescued the afterhyperpolarizing potential (AHP) as well as spike frequency adaptation in epileptic animals, both of which are prominent functions of KCa2 channels.ConclusionThese data indicate that TBB pretreatment prior to SE slows down disease progression during epileptogenesis involving increased KCa2 function, probably due to a persistently decreased CK2 protein expression. |
topic |
temporal lobe epilepsy patch-clamp intracellular recording field potential recording video-EEG monitoring Timm stain |
url |
https://www.frontiersin.org/article/10.3389/fncel.2020.00033/full |
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