Deletion of ephrin-B2 from vGAT neurons in mouse causes social anxiety disorder like phenotypes  

作　　者：JU Pei-jun ZHU Cui-zhen ZHU Cui-zhen CHENG Ying CHEN Jian-hua ZHANG Yu ZHU Xiao-na XU Nan-jie CHEN Jing-hong 

机构地区：[1]Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China,Shanghai Key Laboratory of Psychotic Disorders, Shanghai 201108, China [2]Anhui Mental Health Center, Hefei 230022, China [3]Shanghai Jiao Tong University

出　　处：《中国药理学与毒理学杂志》2018年第9期730-732,共3页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China (81501153;81571326).

摘　　要：OBJECTIVE Social anxiety disorder,also known as social phobia,is the most common of all anxiety disorders.Despite the seriousness of this disorder,it has rarely been studied and as a consequence,little is known about its underlying neurobiology.Growing evidence suggests that inhibitory neurons dysfunction could affect the balance of neuronal activity in psychotic disorders including anxiety,SAD,etc.Ephrin-B(EB) proteins were previously demonstrated to ensure normal distribution and function of inhibitory interneurons in the brain.We thus proposed that deletion of EB2 in inhibitory neurons might destroy the homeostasis of excitatory neurons and inhibitory neurons,and induce behavioral deficits associated with psychotic diseases.METHODS(1)Mice.We generated conditional EB2 knockout mice as a model of SAD and characterized the behaviors and the biochemical changes in the brains of the knockout mice.We also generated a mouse line with a selective deletion of EB2 from vGAT neurons by breeding a v GAT-Cre line with a loxP-flanked alleles in EB2.For EB2 detection,we crossed vGAT-Cre;EphrinB2 loxp/loxp mice with Rosa26-STOP-tdTomato Cre indicator(Ai9) mice to label the vGAT neurons with tdTomato.Mice were maintained in a mixed CD1/129 genetic background.Al experiments involving mice were carried out in accordance with the Shanghai Jiaotong University.Genotypes were unlocked only after completion of analysis.(2) General procedures for behavioral testing.Open field test:Locomotor activity was measured using an open field test.The size of the open field box was 44 cm×44 cm×44 cm.Each mouse was placed in the corner of the open-field apparatus at the beginning of the test,and allowed to explore it for 15 min.The total distance traveled(in cm) and counts for stereotyped behaviors were recorded and analyzed.The total distance traveled was used as an index of locomotor activity.The percentage of center zone entries was considered as anxiety indexes.EPM test:The elevated plus maze apparatus was made of dark gray plastic and compOBJECTIVE Social anxiety disorder,also known as social phobia,is the most common of all anxiety disorders.Despite the seriousness of this disorder,it has rarely been studied and as a consequence,little is known about its underlying neurobiology.Growing evidence suggests that inhibitory neurons dysfunction could affect the balance of neuronal activity in psychotic disorders including anxiety,SAD,etc.Ephrin-B(EB) proteins were previously demonstrated to ensure normal distribution and function of inhibitory interneurons in the brain.We thus proposed that deletion of EB2 in inhibitory neurons might destroy the homeostasis of excitatory neurons and inhibitory neurons,and induce behavioral deficits associated with psychotic diseases.METHODS(1)Mice.We generated conditional EB2 knockout mice as a model of SAD and characterized the behaviors and the biochemical changes in the brains of the knockout mice.We also generated a mouse line with a selective deletion of EB2 from vGAT neurons by breeding a v GAT-Cre line with a loxP-flanked alleles in EB2.For EB2 detection,we crossed vGAT-Cre;EphrinB2 loxp/loxp mice with Rosa26-STOP-tdTomato Cre indicator(Ai9) mice to label the vGAT neurons with tdTomato.Mice were maintained in a mixed CD1/129 genetic background.Al experiments involving mice were carried out in accordance with the Shanghai Jiaotong University.Genotypes were unlocked only after completion of analysis.(2) General procedures for behavioral testing.Open field test:Locomotor activity was measured using an open field test.The size of the open field box was 44 cm×44 cm×44 cm.Each mouse was placed in the corner of the open-field apparatus at the beginning of the test,and allowed to explore it for 15 min.The total distance traveled(in cm) and counts for stereotyped behaviors were recorded and analyzed.The total distance traveled was used as an index of locomotor activity.The percentage of center zone entries was considered as anxiety indexes.EPM test:The elevated plus maze apparatus was made of dark gray plastic and comp

关 键 词：ephrin-B2 social ANXIETY DISORDER 

分 类 号：R[医药卫生]