Syntaxin 7 modulates seizure activity in epilepsy

The exact pathogenesis of epilepsy, one of the most common and devastating diseases of the nervous system, is not fully understood. Syntaxin7 (STX7) is a member of the SNARE superfamily, which mediates membrane fusion events in all cells. However, the role STX7 plays in epilepsy remains unclear. The...

Full description

Bibliographic Details
Main Authors: Junhong Wu, Hui Zhang, Liu Yang, Yuanyuan Chen, Jiyuan Li, Min Yang, Xiaogang Zhang, Changlong He, Xuefeng Wang, Xin Xu
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996123001328
_version_ 1797827772919316480
author Junhong Wu
Hui Zhang
Liu Yang
Yuanyuan Chen
Jiyuan Li
Min Yang
Xiaogang Zhang
Changlong He
Xuefeng Wang
Xin Xu
author_facet Junhong Wu
Hui Zhang
Liu Yang
Yuanyuan Chen
Jiyuan Li
Min Yang
Xiaogang Zhang
Changlong He
Xuefeng Wang
Xin Xu
author_sort Junhong Wu
collection DOAJ
description The exact pathogenesis of epilepsy, one of the most common and devastating diseases of the nervous system, is not fully understood. Syntaxin7 (STX7) is a member of the SNARE superfamily, which mediates membrane fusion events in all cells. However, the role STX7 plays in epilepsy remains unclear. Therefore, this study investigates the role of STX7 in epilepsy. Our study found that the expression of STX7 was reduced in the epileptic brain and that overexpression of STX7 decreased the susceptibility to epileptic seizures and alleviated epileptic activity in a kainic acid–induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the downregulation of STX7 showed opposite effects. Whole-cell patch-clamp recordings showed that STX7 does not affect the intrinsic excitability of neurons, but rather the excitation/inhibition ratio mediated by affecting the release of presynaptic γ-aminobutyric acid neurotransmitters. Transmission electron microscopy results showed that STX7 did not affect the density of inhibitory synapses but could affect the density of inhibitory vesicles. Taken together, these results reveal a previously unknown function of STX7 in epilepsy and suggest that STX7 may serve as a novel target for epilepsy therapy.
first_indexed 2024-04-09T12:53:44Z
format Article
id doaj.art-5c413e7d99d74a098462d8d91331af13
institution Directory Open Access Journal
issn 1095-953X
language English
last_indexed 2024-04-09T12:53:44Z
publishDate 2023-06-01
publisher Elsevier
record_format Article
series Neurobiology of Disease
spelling doaj.art-5c413e7d99d74a098462d8d91331af132023-05-14T04:28:10ZengElsevierNeurobiology of Disease1095-953X2023-06-01181106118Syntaxin 7 modulates seizure activity in epilepsyJunhong Wu0Hui Zhang1Liu Yang2Yuanyuan Chen3Jiyuan Li4Min Yang5Xiaogang Zhang6Changlong He7Xuefeng Wang8Xin Xu9Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, ChinaDepartment of Neurology, The First Hospital of Shanxi Medical University, No.85 Jiefang South Road, Taiyuan, Shanxi Province, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China; Department of Neurology, Chongqing General Hospital, Chongqing Key Laboratory of Neurodegenerative Diseases, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing 401147, ChinaDepartment of Laboratory Medicine, People's Hospital of Jiulongpo District, Chongqing 400016, China; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China; Corresponding author at: Department of Laboratory Medicine, People's Hospital of Jiulongpo District, Chongqing 40016, China.Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China; Corresponding authors.Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China; Corresponding authors.The exact pathogenesis of epilepsy, one of the most common and devastating diseases of the nervous system, is not fully understood. Syntaxin7 (STX7) is a member of the SNARE superfamily, which mediates membrane fusion events in all cells. However, the role STX7 plays in epilepsy remains unclear. Therefore, this study investigates the role of STX7 in epilepsy. Our study found that the expression of STX7 was reduced in the epileptic brain and that overexpression of STX7 decreased the susceptibility to epileptic seizures and alleviated epileptic activity in a kainic acid–induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the downregulation of STX7 showed opposite effects. Whole-cell patch-clamp recordings showed that STX7 does not affect the intrinsic excitability of neurons, but rather the excitation/inhibition ratio mediated by affecting the release of presynaptic γ-aminobutyric acid neurotransmitters. Transmission electron microscopy results showed that STX7 did not affect the density of inhibitory synapses but could affect the density of inhibitory vesicles. Taken together, these results reveal a previously unknown function of STX7 in epilepsy and suggest that STX7 may serve as a novel target for epilepsy therapy.http://www.sciencedirect.com/science/article/pii/S0969996123001328Syntaxin 7EpilepsySynaptic transmissionSynaptic vesicleGABA
spellingShingle Junhong Wu
Hui Zhang
Liu Yang
Yuanyuan Chen
Jiyuan Li
Min Yang
Xiaogang Zhang
Changlong He
Xuefeng Wang
Xin Xu
Syntaxin 7 modulates seizure activity in epilepsy
Neurobiology of Disease
Syntaxin 7
Epilepsy
Synaptic transmission
Synaptic vesicle
GABA
title Syntaxin 7 modulates seizure activity in epilepsy
title_full Syntaxin 7 modulates seizure activity in epilepsy
title_fullStr Syntaxin 7 modulates seizure activity in epilepsy
title_full_unstemmed Syntaxin 7 modulates seizure activity in epilepsy
title_short Syntaxin 7 modulates seizure activity in epilepsy
title_sort syntaxin 7 modulates seizure activity in epilepsy
topic Syntaxin 7
Epilepsy
Synaptic transmission
Synaptic vesicle
GABA
url http://www.sciencedirect.com/science/article/pii/S0969996123001328
work_keys_str_mv AT junhongwu syntaxin7modulatesseizureactivityinepilepsy
AT huizhang syntaxin7modulatesseizureactivityinepilepsy
AT liuyang syntaxin7modulatesseizureactivityinepilepsy
AT yuanyuanchen syntaxin7modulatesseizureactivityinepilepsy
AT jiyuanli syntaxin7modulatesseizureactivityinepilepsy
AT minyang syntaxin7modulatesseizureactivityinepilepsy
AT xiaogangzhang syntaxin7modulatesseizureactivityinepilepsy
AT changlonghe syntaxin7modulatesseizureactivityinepilepsy
AT xuefengwang syntaxin7modulatesseizureactivityinepilepsy
AT xinxu syntaxin7modulatesseizureactivityinepilepsy