Desipramine reverses remote memory deficits by activating calmodulin- CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome

作     者：Lei Chen Yuting Li Minggang Liu Zhaohui Lan Xu Zhang Xiujuan Yang Qian Zhao Shuai Wang Longyong Xu Ying Zhou Yifang Kuang Tatsuo Suzuki Katsuhiko Tabuchi Eiki Takahashi Miou Zhou Charlie Degui Chen Tianle Xu Weidong Li 

作者机构：Bio-X InstitutesKey Laboratory for the Genetics of Development and Neuropsychiatric Disorders(Ministry of Education)Brain Health and Brain Technology Center at Global Institute of Future TechnologyInstitute of Psychology and Behavioral ScienceShanghai Jiao Tong UniversityShanghaiChina Department of Anatomy and PhysiologyShanghai Jiao Tong University School of MedicineShanghaiChina institute of Mental Health and Drug DiscoveryOujiang LaboratoryWenzhouZhejiangChina Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina Shinshu University School of MedicineNaganoJapan western University of Health SciencesPomonaCaliforniaUSA WLA LaboratoriesWorld Laureates AssociationShanghaiChina 

出 版 物：《General Psychiatry》 (综合精神医学（英文）)

年 卷 期：2024年第37卷第5期

页      面：522-531页

核心收录：

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：supported by STI2030-Major Projects(2022ZD0204900) the National Natural Science Foundation of China(NSFC)(91632103,31900732,31771157) the Program of Shanghai Subject Chief Scientist(17XD1401700) National Key Research and Development Program of China(2018YFE0126700) the Shanghai Education Commission Research and Innovation Program(2019-01-07-00-02-E00037) Natural Science Foundation of Chongqing cstc2021jcyjmsxmX1176,the‘111’Program of Higher Education Discipline Innovation,‘Eastern Scholar’(Shanghai Municipal Education Commission),Shanghai Municipal Commission of Science and Technology Program(21dz2210100) China Postdoctoral Science Foundation(202N1702133,2021M702137) The National Science Fund for Distinguished Young Scholars(31900732) 

主　　题：impaired reversed UTX 

摘      要：Background Kabukisyndrome(KS)is arare developmental disorder characterised by multiple congenital anomalies and intellectual ***(ubiquitously transcribed tetratricopeptide repeat,X chromosome),which encodes a histone demethylase,is one of the two major pathogenic risk genes for *** intellectual disability is a key phenotype of KS,the role of UTX in cognitive function remains ***,no targeted therapies are available for *** This study aimed to investigate how UTX regulates cognition,to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for *** WegeneratedUTXconditional knockoutmice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3(trimethylated histone H3 at lysine 27)*** UTX-knockout mice showeddecreased phosphorylation of calcium/calmodulin-dependent protein kinase I,impaired long-term potentiation and deficit in remote contextual fear *** effects were reversed by an Food and Drug Administration-approved drug *** Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function,and suggest that desipramine could be a potential treatment for KS.