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Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model
Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. Howeve...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976828/ https://www.ncbi.nlm.nih.gov/pubmed/24757570 http://dx.doi.org/10.1155/2014/310146 |
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author | Kong, Shuzhen Cheng, Zhihua Liu, Jianhui Wang, Yun |
author_facet | Kong, Shuzhen Cheng, Zhihua Liu, Jianhui Wang, Yun |
author_sort | Kong, Shuzhen |
collection | PubMed |
description | Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future. |
format | Online Article Text |
id | pubmed-3976828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-39768282014-04-22 Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model Kong, Shuzhen Cheng, Zhihua Liu, Jianhui Wang, Yun Neural Plast Research Article Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future. Hindawi Publishing Corporation 2014 2014-03-13 /pmc/articles/PMC3976828/ /pubmed/24757570 http://dx.doi.org/10.1155/2014/310146 Text en Copyright © 2014 Shuzhen Kong et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kong, Shuzhen Cheng, Zhihua Liu, Jianhui Wang, Yun Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title | Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title_full | Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title_fullStr | Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title_full_unstemmed | Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title_short | Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model |
title_sort | downregulated gaba and bdnf-trkb pathway in chronic cyclothiazide seizure model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976828/ https://www.ncbi.nlm.nih.gov/pubmed/24757570 http://dx.doi.org/10.1155/2014/310146 |
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