Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice

doi:10.1016/j.nbd.2024.106457

科研成果详情

题名	Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice
作者	Deng, Lu1; Jiang, Hong2; Lin, Jingjing 2; Xu, Di1; Qi, Ailin2; Guo, Qing2; Li, Ping-Ping3; Wang, Xinshi4; Liu, Judy S.5; Fu, Xiaoqin3; Li, Peijun1,2,6
发表日期	2024-04
发表期刊	Neurobiology of disease 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	ARC CLOCK Epilepsy Inhibitory neurons
其他关键词	LONG-TERM POTENTIATION ; NEUROTROPHIC FACTOR ; SYNAPTIC PLASTICITY ; PROTEIN EXPRESSION ; ARC ; ARC/ARG3.1 ; HIPPOCAMPUS ; SEIZURES ; GENE ; CONSOLIDATION
摘要	Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clockflox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clockflox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy
资助项目	National Natural Science Foundation of China[81871035,81971425,82001363,82071378];Natural Science Foundation of Zhejiang Province[LZ19H090001];
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN	0969-9961
EISSN	1095-953X
卷号	193
DOI	10.1016/j.nbd.2024.106457
页数	11
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:001208231900001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38423191
SCOPUSEID	2-s2.0-85186498858
通讯作者地址	[Li, Peijun]Department of Geriatrics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China ; [Liu, Judy S.]Department of Neurology,Department of Molecular Biology,Cell Biology,and Biochemistry,Brown University,Providence,02903,United States
Scopus学科分类	Neurology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210174
专题	第二临床医学院，附属第二医院、育英儿童医院第二临床医学院，附属第二医院、育英儿童医院_神经病学_神经内科第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
通讯作者	Liu, Judy S.; Fu, Xiaoqin; Li, Peijun
作者单位	1.Department of Geriatrics,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China; 2.Department of Neurology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 3.Department of Neonatology,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China; 4.Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Shangcai Village, Ouhai District,Wenzhou,China; 5.Department of Neurology,Department of Molecular Biology,Cell Biology,and Biochemistry,Brown University,Providence,02903,United States; 6.Institute of Brain Science and Brain-inspired Research,Shandong First Medical University & Shandong Academy of Medical Sciences,Shandong,Jinan,250117,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Deng, Lu,Jiang, Hong,Lin, Jingjing,et al. Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice[J]. Neurobiology of disease,2024,193.
APA	Deng, Lu., Jiang, Hong., Lin, Jingjing., Xu, Di., Qi, Ailin., ... & Li, Peijun. (2024). Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice. Neurobiology of disease, 193.
MLA	Deng, Lu,et al."Clock knockout in inhibitory neurons reduces predisposition to epilepsy and influences anxiety-like behaviors in mice".Neurobiology of disease 193(2024).