检索结果-南通市图书馆

Graded and pan-neural disease phenotypes of rett syndrome linked with dosage of functional MeCP2

Protein & Cell 2021年第8期12卷 639-652页

作者： Xiaoying Chen Xu Han Bruno Bianchi Wuqiang Guan Weihong Ge Yong-Chun Yu Yi E.Sun Shanghai Institute of Stem Cell Research and Clinical Translation Shanghai East HospitalTongji University School of MedicineShanghai 200120China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceJing’an District Centre Hospital of ShanghaiFudan UniversityShanghai 200032China Department of Psychiatry and Biobehavioral Sciences David Geffen School of MedicineUCLALos AngelesCA 90095USA

rett syndrome(RTT)is a progressive neurodevelop-mental disorder,mainly caused by mutations in MeCP2 and currently with no *** report here that neurons from R106W MeCP2 RTT human iPSCs as well as human embryonic stem cells after MeCP2 knockdown exhibit consistent and long-lasting impairment in maturation as indicated by impaired action potentials and passive membrane properties as well as reduced soma size and spine ***,RTT-inherent defects in neuronal maturation could be pan-neuronal and occurred in neurons with both dorsal and ventral forebrain *** of MeCP2 led to more severe neuronal deficits as compared to RTT iPSC-derived neurons,which appeared to retain partial ***,consistent deficits in nuclear size,dendritic complexity and circuitry-dependent spontaneous postsynaptic currents could only be observed in MeCP2 knockdown neurons but not RTT iPSC-derived *** neuron-intrinsic and circuitry-dependent deficits of MeCP2-deficient neurons could be fully or partially rescued by re-expression of wild type or T158M MeCP2,strengthening the dosage dependency of MeCP2 on disease phenotypes and also the partial function of the *** findings thus reveal stable neuronal maturation deficits and unexpectedly,graded sensitivities of neuron-inherent and neural transmission phenotypes towards the extent of MeCP2 deficiency,which is informative for future therapeutic development.

关键词： MeCP2 rett syndrome human pluripotent stem cell neural differentiation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Functional Recovery with Electro-Acupuncture Stimulation in an Mecp2-Knockout Rat Model of rett syndrome

引用

Engineering 2022年第5期8卷 83-89页

作者： Yanhong Sun Zhifang Chen Yi Xu Yuefang Zhang Zhilei Ge Chenglie Lin Yi Zhou Fangfei Zhao Meiling Yan Xinyi Liu Ying Zhu Jimin Gao Hongyi Li Lihua Wang Jun Hu Zilong Qiu Chunhai Fan Bioimaging Center Shanghai Synchrotron Radiation FacilityZhang Jiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Division of Physical Biology CAS Key Laboratory of Interfacial Physics and TechnologyShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201800China Institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China College of Basic Medicine Chengdu University of Traditional Chinese MedicineChengdu 611137China Cardiology Department Beijing HospitalBeijing 100730China

rett syndrome is a progressive neurodevelopmental disorder that lacks effective *** deep-brain stimulation can alleviate some symptoms in rett model mice,this interventional manipula-tion requires deliberate surgical ***,we report that electro-acupuncture stimulation(EAS)can ameliorate symptoms of an Mecp2-knockout rat model of rett syndrome from the remote acupoints Baihui(GV 20),Yongquan(KI 1),and Shenmen(HT 7).We find that EAS not only prolongs the survival time of rett rats,but also improves their behavior ability,including locomotion,motor coordination,and social *** activation was observed in the substantia nigra of the midbrain,corpus striatum,and cerebral cortex of wild-type and rett model rats,as reflected by the increased expression of the c-Fos ***,EAS provides a potential promising therapeutic tool for treating neurodevel-opmental diseases.

关键词： Neurodevelopmental disorder Electro-acupuncture stimulation rett syndrome Motor function Social interaction

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Advances in the pathogenesis of rett syndrome using cell models

引用

Animal Models and Experimental Medicine 2022年第6期5卷 532-541页

作者： Sijia Lu Yongchang Chen Zhengbo Wang State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingChina Yunnan Key Laboratory of Primate Biomedical Research KunmingChina

rett syndrome(RTT)is a progressive neurodevelopmental disorder that occurs mainly in girls with a range of typical symptoms of autism spectrum ***2 protein loss-of-function in neural lineage cells is the main cause of RTT *** it is still hard to understand the mechanism of RTT on the basis of only clinical patients or animal models,cell models cultured in vitro play indispensable *** we reviewed the research progress in the pathogenesis of RTT at the cellular level,summarized the preclinical-research-related applications,and prospected potential future development.

关键词： cell models MeCP2 pathogenesis rett syndrome

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

The neural circuit basis of rett syndrome

引用

Frontiers of physics 2012年第5期7卷 428-435页

作者： Darren GOFFIN Zhaolan (Joe) ZHOU Department of Genetics University of Pennsylvania School of Medicine 450 Clinical Research Building 415 Curie Boulevard PhiladelphiaPA 19104 USA

rett syndrome is an Autism Spectrum Disorder caused by mutations in the gene encoding methyl-CpG binding protein （MeCP2）. Following a period of normal development, patients lose learned communication and motor skills, and develop a number of symptoms including motor disturbances, cognitive impairments and often seizures. In this review, we discuss the role of MeCP2 in regulating synaptic function and how synaptic dysfunctions lead to neuronal network impairments and alterations in sensory information processing. We propose that rett syndrome is a disorder of neural circuits as a result of non-linear accumulated dysfunction of synapses at the level of individual cell populations across multiple neurotransmitter systems and brain regions.

关键词： rett syndrome MeCP2 neural circuit ERP synapse

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Circuitry-dependent and independent phenotypes of MeCP2-deficient human neurons derived from ESCs and rett syndrome specific iPSCs

Circuitry-dependent and independent phenotypes of MeCP2-defi...

引用

中国神经科学学会第十届全国学术会议

作者： Xiao-Ying Chen Xu Han Bruno CF Blanchi Yi Eve Sun Yong-Chun Yu Translational Center for Stem Cell Research Tongji HospitalStem Cell Research CenterTongji University School of Medicine Institute of Neurobiology Institute of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University Intellectual and Developmental Disabilities Research Center Departments of Psychiatry & Behavioral Sciences and Molecular & Medical PharmacologySemel Institute for NeuroscienceDavid Geffen School of Medicine at University of California Los Angeles635 Charles E.Young Dr.South

It becomes increasingly acknowledged that changes in synaptic transmission and/or neural network properties are regional- and circuitry-specific in many neurological *** feature poses a huge challenge for using patient-specific induced pluripotent stem cells（hiPSCs） to model neurological disorders,because currently,scientists have limited control over the context of the various neural networks formed in such "disease-in-a-dish" ***,we report that neurons derived from rett syndrome（RTT） hiPSCs exhibit variable spontaneous postsynaptic currents and variable ratios between excitation-inhibition from culture to *** alterations of circuitry contents using a ventralizing agent changed neural transmission phenotype,suggesting a circuitry-specific nature of such *** contrast,cell-intrinsic electrophysiological and morphological properties of RTT neurons demonstrate consistent changes,regardless of the type of circuitries *** findings demonstrate that "disease-in-a-dish" models using hiPSC-derived neurons,while may capture cell-intrinsic properties of diseased neurons,could be rather limited for assessing neural-circuitry-dependent phenotypes.

关键词： circuitry rett syndrome hiPSCs

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

瑞特综合征（rett syndrome）的分子和突触机制

瑞特综合征（Rett Syndrome）的分子和突触机制

引用

中国神经科学学会第十届全国学术会议

作者： Zhi-Qi Xiong Institute of Neuroscience the Chinese Academy of Sciences

rett syndrome is a severe neurodevelopmental disorder that primarily affects *** features a range of neuropsychiatric abnormalities including motor dysfunctions and mild to severe cognitive *** mutations in Methyl-CpG Binding Protein 2（MECP2） or Cychn-Dependent-Kinase Like 5（CDKlS） cause classic rett syndrome and related variants with similar ***2 functions as a transcriptional repressor involved in neuronal development and synaptic *** recent studies showed that CDKL5 also plays important roles in neuronal development such as neurite growth and dendritic spine *** mature neurons,PSD-95 interacts with CDKL5 in a palmitoylation-dependent fashion and regulates its targeting to excitatory ***,certain disease-associated mutations which abolish this interaction reduce synaptic localization of ***,disruption of this interaction diminishes synaptic targeting of CDKL5 and inhibits dendritic spine growth and synaptic ***,our findings reveal an unexpected role of palmitoylated PSD-95 in synaptic targeting of CDKL5,which may represent a novel mechanism for synaptic dysfunction in rett syndrome.

关键词： rett syndrome MeCP2 CDKL5 synaptic transmission

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Generation of a monkey with MECP2 mutations by TALEN-based gene targeting

引用

Neuroscience Bulletin 2014年第3期30卷 381-386页

作者： Zhen Liu Xue Zhou Ying Zhu Zhi-Fang Chen Bin Yu Yan Wang Chen-Chen Zhang Yan-Hong Nie Xiao Sang Yi-Jun Cai Yue-Fang Zhang Chen Zhang Wen-Hao Zhou Qiang Sun Zilong Qiu Institute of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Department of Neonatology Children’s Hospital of Fudan University State Key Laboratory of Biomembrane and Membrane Biotechnology School of Life Sciences PKU-IDG/McGovern Institute for Brain Research Peking University

Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey （Macaca fascicularis） carrying MECP2 mutations using transcription activator-like effector nucleases （TALENs）-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frame- shifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey＇s brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.

关键词： monkey TALEN MeCP2 rett syndrome

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Deep learning-based activity recognition and fine motor identification using 2D skeletons of cynomolgus monkeys

引用

动物学研究(英文) 2023年第5期44卷 967-980页

作者： Chuxi Li Zifan Xiao Yerong Li Zhinan Chen Xun Ji Yiqun Liu Shufei Feng Zhen Zhang Kaiming Zhang Jianfeng Feng Trevor W.Robbins Shisheng Xiong Yongchang Chen Xiao Xiao School of Information Science and Technology Micro Nano System Center Fudan UniversityShanghai 200433China Department of Anesthesiology Huashan HospitalKey Laboratory of Computational Neuroscience and Brain-Inspired IntelligenceMinistry of EducationBehavioral and Cognitive Neuroscience CenterInstitute of Science and Technology for Brain-Inspired IntelligenceMOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200433China Kuang Yaming Honors School Nanjing UniversityNanjingJiangsu 210023China Shanghai Key Laboratory of Intelligent Information Processing School of Computer ScienceFudan UniversityShanghai 200433China State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China New Vision World LLC. Aliso ViejoCalifornia 92656USA Behavioural and Clinical Neuroscience Institute University of CambridgeCambridgeCB21TNUK

Video-based action recognition is becoming a vital tool in clinical research and neuroscientific study for disorder detection and ***,action recognition currently used in non-human primate(NHP)research relies heavily on intense manual labor and lacks standardized *** this work,we established two standard benchmark datasets of NHPs in the laboratory:Monkeyin Lab(Mi L),which includes 13 categories of actions and postures,and MiL2D,which includes sequences of two-dimensional(2D)skeleton ***,based on recent methodological advances in deep learning and skeleton visualization,we introduced the Monkey Monitor Kit(Mon Kit)toolbox for automatic action recognition,posture estimation,and identification of fine motor activity in *** the datasets and Mon Kit,we evaluated the daily behaviors of wild-type cynomolgus monkeys within their home cages and experimental environments and compared these observations with the behaviors exhibited by cynomolgus monkeys possessing mutations in the MECP2 gene as a disease model of rett syndrome(RTT).Mon Kit was used to assess motor function,stereotyped behaviors,and depressive phenotypes,with the outcomes compared with human manual *** Kit established consistent criteria for identifying behavior in NHPs with high accuracy and efficiency,thus providing a novel and comprehensive tool for assessing phenotypic behavior in monkeys.

关键词： Action recognition Fine motor identification Two-stream deep model 2D skeleton Non-human primates rett syndrome

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

MeCP2:multifaceted roles in gene regulation and neural development

引用

Neuroscience Bulletin 2014年第4期30卷 601-609页

作者： Tian-Lin Cheng Zilong Qiu Institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences

Methyl-CpG-binding protein 2 （MeCP2） is a classic methylated-DNA-binding protein, dysfunctions of which lead to various neurodevelopmental disorders such as rett syndrome and autism spectrum disorder. Initially recognized as a transcriptional repressor, MeCP2 has been studied extensively and its functions have been expanded dramatically in the past two decades. Recently, it was found to be involved in gene regulation at the post-transcriptional level. MeCP2 represses nuclear microRNA processing by interacting directly with the Drosha/DGCR8 complex. In addition to its multifaceted functions, MeCP2 is remarkably modulated by post- translational modifications such as phosphorylation, SUMOylation, and acetylation, providing more regulatory dimensions to its functions. The role of MeCP2 in the central nervous system has been studied extensively, from neurons to glia. Future investigations combining molecular, cellular, and physiological methods are necessary for defining the roles of MeCP2 in the brain and developing efficient treatments for MeCP2-related brain disorders.

关键词： MeCP2 rett syndrome central nervous system gene expression regulation post-translationalmodification post-transcriptional regulation glia

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Structural investigation of rett-inducing MeCP2 mutations

引用

Genes & Diseases 2019年第1期6卷 31-34页

作者： Ottavia Spiga Simone Gardini Nicole Rossi Vittoria Cicaloni Francesco Pettini Neri Niccolai Annalisa Santucci Department of Biotechnology Chemistry and PharmacyUniversity of SienaSiena53100Italy GenomeUp SRL Rome00199Italy Toscana Life Sciences Foundation(TLS) Siena 53100Italy

X-ray structure of methyl-CpG binding domain(MBD)of MeCP2,an intrinsically disordered protein(IDP)involved in rett syndrome,offers a rational basis for defining the spatial distribution for most of the sites where mutations responsible of rett syndrome,RTT,*** have ascribed pathogenicity for mutations of amino acids bearing positively charged side chains,all located at the protein-DNA interface,as positive charge removal cause reduction of the MeCP2-DNA adduct *** of the frequent proline replacements,outside the DNA contact moiety of MBD,can be attributed to the role of this amino acid for maintaining both unfolded states for unbound MeCP2 and,at the same time,to favor some higher conformational order for stabilizing structural determinants required by protein *** hypotheses can be extended to transcription repressor domain,TRD,the other MeCP2-DNA interaction site and,in general,to all the IDP that interact with nucleic acids.

关键词： DNA binding domains MeCP2 Mutation distribution Protein structure rett syndrome

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：