PMID- 37031804 OWN - NLM STAT- MEDLINE DCOM- 20230517 LR - 20230519 IS - 1095-953X (Electronic) IS - 0969-9961 (Linking) VI - 181 DP - 2023 Jun 1 TI - Syntaxin 7 modulates seizure activity in epilepsy. PG - 106118 LID - S0969-9961(23)00132-8 [pii] LID - 10.1016/j.nbd.2023.106118 [doi] AB - 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 gamma-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. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Wu, Junhong AU - Wu J AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. FAU - Zhang, Hui AU - Zhang H AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. FAU - Yang, Liu AU - Yang L AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. FAU - Chen, Yuanyuan AU - Chen Y AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. FAU - Li, Jiyuan AU - Li J AD - Department of Neurology, The First Hospital of Shanxi Medical University, No.85 Jiefang South Road, Taiyuan, Shanxi Province, China. FAU - Yang, Min AU - Yang M AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. FAU - Zhang, Xiaogang AU - Zhang X AD - Department 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, China. FAU - He, Changlong AU - He C AD - Department 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. Electronic address: 282702575@qq.com. FAU - Wang, Xuefeng AU - Wang X AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. Electronic address: xfyp@163.com. FAU - Xu, Xin AU - Xu X AD - Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China. Electronic address: xuxin86516@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230407 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Carrier Proteins) RN - 0 (Qa-SNARE Proteins) SB - IM MH - Humans MH - Carrier Proteins MH - *Epilepsy/metabolism MH - Neurons/metabolism MH - Qa-SNARE Proteins/metabolism MH - Seizures/metabolism MH - Animals MH - Mice OTO - NOTNLM OT - Epilepsy OT - GABA OT - Synaptic transmission OT - Synaptic vesicle OT - Syntaxin 7 COIS- Declaration of Competing Interest None. EDAT- 2023/04/10 06:00 MHDA- 2023/05/17 06:42 CRDT- 2023/04/09 19:24 PHST- 2023/01/31 00:00 [received] PHST- 2023/03/18 00:00 [revised] PHST- 2023/04/05 00:00 [accepted] PHST- 2023/05/17 06:42 [medline] PHST- 2023/04/10 06:00 [pubmed] PHST- 2023/04/09 19:24 [entrez] AID - S0969-9961(23)00132-8 [pii] AID - 10.1016/j.nbd.2023.106118 [doi] PST - ppublish SO - Neurobiol Dis. 2023 Jun 1;181:106118. doi: 10.1016/j.nbd.2023.106118. Epub 2023 Apr 7.