TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice
- Autores
- Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.
Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados Unidos
Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos - Materia
-
Beta Rhythm
Electroencephalography
Gamma Rhythm
Seizures
Spectral Analysis
Transient Receptor Potential Channels - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/47700
Ver los metadatos del registro completo
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TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in micePhelan, Kevin D.Shwe, U ThaungCozart, Michael A.Wu, HongMock, Matthew M.Abramowitz, JoelBirnbaumer, LutzZheng, FangBeta RhythmElectroencephalographyGamma RhythmSeizuresSpectral AnalysisTransient Receptor Potential Channelshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados UnidosFil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados UnidosFil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados UnidosFil: Wu, Hong. University of Arkansas for Medical Sciences; Estados UnidosFil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados UnidosFil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados UnidosWiley Blackwell Publishing, Inc2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47700Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-2540013-9580CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/epi.13648info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.13648info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:26Zoai:ri.conicet.gov.ar:11336/47700instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:48:26.94CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
title |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
spellingShingle |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice Phelan, Kevin D. Beta Rhythm Electroencephalography Gamma Rhythm Seizures Spectral Analysis Transient Receptor Potential Channels |
title_short |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
title_full |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
title_fullStr |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
title_full_unstemmed |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
title_sort |
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice |
dc.creator.none.fl_str_mv |
Phelan, Kevin D. Shwe, U Thaung Cozart, Michael A. Wu, Hong Mock, Matthew M. Abramowitz, Joel Birnbaumer, Lutz Zheng, Fang |
author |
Phelan, Kevin D. |
author_facet |
Phelan, Kevin D. Shwe, U Thaung Cozart, Michael A. Wu, Hong Mock, Matthew M. Abramowitz, Joel Birnbaumer, Lutz Zheng, Fang |
author_role |
author |
author2 |
Shwe, U Thaung Cozart, Michael A. Wu, Hong Mock, Matthew M. Abramowitz, Joel Birnbaumer, Lutz Zheng, Fang |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Beta Rhythm Electroencephalography Gamma Rhythm Seizures Spectral Analysis Transient Receptor Potential Channels |
topic |
Beta Rhythm Electroencephalography Gamma Rhythm Seizures Spectral Analysis Transient Receptor Potential Channels |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs. Fil: Phelan, Kevin D.. University of Arkansas for Medical Sciences; Estados Unidos Fil: Shwe, U Thaung. University of Arkansas for Medical Sciences; Estados Unidos Fil: Cozart, Michael A.. University of Arkansas for Medical Sciences; Estados Unidos Fil: Wu, Hong. University of Arkansas for Medical Sciences; Estados Unidos Fil: Mock, Matthew M.. University of Arkansas for Medical Sciences; Estados Unidos Fil: Abramowitz, Joel. National Institute of Environmental Health Sciences; Estados Unidos Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institute of Environmental Health Sciences; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina Fil: Zheng, Fang. University of Arkansas for Medical Sciences; Estados Unidos |
description |
Objective: Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the brain-derived neurotrophic factor (BDNF)/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced status epilepticus (SE). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity, which dominates both the preictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/47700 Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-254 0013-9580 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/47700 |
identifier_str_mv |
Phelan, Kevin D.; Shwe, U Thaung; Cozart, Michael A.; Wu, Hong; Mock, Matthew M.; et al.; TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice; Wiley Blackwell Publishing, Inc; Epilepsia; 58; 2; 2-2017; 247-254 0013-9580 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1111/epi.13648 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.13648 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613505016135680 |
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13.070432 |