典型文献
Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling
文献摘要：
Major depressive disorder(MDD)is a common psychiatric disorder characterized by persistent mood despondency and loss of motivation.Although numerous hypotheses have been proposed,the possible pathogenesis of MDD remains unclear.Several recent studies show that a classic transporter protein,sortilin,is closely associated with depression.In the present study,we investigated the role of sortilin in MDD using a well-established rodent model of depression.Mice were subjected to chronic unpredictable mild stress(CUMS)for 6 weeks.We showed that the expression levels of sortilin were significantly increased in the prefrontal cortex and hippocampus of CUMS mice.The depressive-like behaviors induced by CUMS were alleviated by specific knockdown of sortilin in the prefrontal cortex and hippocampus.We revealed that sortilin facilitated acid sphingomyelinase(ASM)/ceramide signaling,which activated RhoA/ROCK2 signaling,ultimately causing the transformation of dendritic spine dynamics.Specific overexpression of sortilin in the prefrontal cortex and hippocampus induced depressive-like behaviors,which was mitigated by injection of ASM inhibitor SR33557(4 μg/μL)into the prefrontal cortex and hippocampus.In conclusion,sortilin knockdown in the prefrontal cortex and hippocampus plays an important role in ameliorating depressive-like behavior induced by CUMS,which is mainly evidenced by decreasing the trafficking of ASM from the trans-Golgi network to the lysosome and reducing the ceramide levels.Our results provide a new insight into the pathology of depression,and demonstrate that sortilin may be a potential therapeutic target for MDD.
文献关键词：
中图分类号：
作者姓名：
Shu-jian Chen;Cong-cong Gao;Qun-yu Lv;Meng-qi Zhao;Xiao-ying Qin;Hong Liao
作者机构：
New Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing 210009,China
文献出处：
引用格式：
[1]Shu-jian Chen;Cong-cong Gao;Qun-yu Lv;Meng-qi Zhao;Xiao-ying Qin;Hong Liao-.Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling)[J].中国药理学报（英文版）,2022(08):1940-1954
A类：
despondency,sphingomyelinase,SR33557
B类：
Sortilin,deletion,prefrontal,cortex,hippocampus,ameliorates,depressive,like,behaviors,mice,regulating,ASM,ceramide,signaling,Major,disorder,MDD,common,psychiatric,characterized,by,persistent,mood,loss,motivation,Although,numerous,hypotheses,have,been,proposed,possible,pathogenesis,remains,unclear,Several,recent,studies,that,classic,transporter,protein,sortilin,closely,associated,depression,In,present,study,investigated,role,well,established,rodent,model,Mice,were,subjected,chronic,unpredictable,mild,stress,CUMS,weeks,We,showed,levels,significantly,increased,induced,alleviated,specific,knockdown,revealed,facilitated,acid,which,activated,RhoA,ROCK2,ultimately,causing,transformation,dendritic,spine,dynamics,Specific,overexpression,was,mitigated,injection,inhibitor,into,conclusion,plays,important,ameliorating,mainly,evidenced,decreasing,trafficking,from,Golgi,network,lysosome,reducing,Our,results,provide,new,insight,pathology,demonstrate,may,potential,therapeutic,target
AB值：
0.507361
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
