Neuron最新文献_第3页

White matter aging and its impact on brain function. 白质老化及其对大脑功能的影响

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.019

Janos Groh, Mikael Simons

引用次数: 0

Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme. 在癌症-神经界面调节钾离子通道可增强致痫性多形性胶质母细胞瘤的神经元兴奋性。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.016

Ye Zhang, Wei Duan, Lingchao Chen, Junrui Chen, Wei Xu, Qi Fan, Shuwei Li, Yuandong Liu, Shidi Wang, Quansheng He, Xiaohui Li, Yang Huang, Haibao Peng, Jiaxu Zhao, Qiangqiang Zhang, Zhixin Qiu, Zhicheng Shao, Bo Zhang, Yihua Wang, Yang Tian, Yousheng Shu, Zhiyong Qin, Yudan Chi

{"title":"Potassium ion channel modulation at cancer-neural interface enhances neuronal excitability in epileptogenic glioblastoma multiforme.","authors":"Ye Zhang, Wei Duan, Lingchao Chen, Junrui Chen, Wei Xu, Qi Fan, Shuwei Li, Yuandong Liu, Shidi Wang, Quansheng He, Xiaohui Li, Yang Huang, Haibao Peng, Jiaxu Zhao, Qiangqiang Zhang, Zhixin Qiu, Zhicheng Shao, Bo Zhang, Yihua Wang, Yang Tian, Yousheng Shu, Zhiyong Qin, Yudan Chi","doi":"10.1016/j.neuron.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.016","url":null,"abstract":"The central nervous system (CNS) is increasingly recognized as a critical modulator in the oncogenesis of glioblastoma multiforme (GBM), with interactions between cancer and local neuronal circuits frequently leading to epilepsy; however, the relative contributions of these factors remain unclear. Here, we report a coordinated intratumor shift among distinct cancer subtypes within progenitor-like families of epileptic GBM patients, revealing an accumulation of oligodendrocyte progenitor (OPC)-like subpopulations at the cancer-neuron interface along with heightened electrical signaling activity in the surrounding neuronal networks. The OPC-like cells associated with epilepsy express KCND2, which encodes the voltage-gated K+ channel KV4.2, enhancing neuronal excitability via accumulation of extracellular K+, as demonstrated in patient-derived ex vivo slices, xenografting models, and engineering organoids. Together, we uncovered the essential local circuitry, cellular components, and molecular mechanisms facilitating cancer-neuron interaction at peritumor borders. KCND2 plays a crucial role in mediating nervous system-cancer electrical communication, suggesting potential targets for intervention.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From animal models to human individuality: Integrative approaches to the study of brain plasticity. 从动物模型到人类个性：研究大脑可塑性的综合方法。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-10-25 DOI: 10.1016/j.neuron.2024.10.006

Maike Hille, Simone Kühn, Gerd Kempermann, Tobias Bonhoeffer, Ulman Lindenberger

{"title":"From animal models to human individuality: Integrative approaches to the study of brain plasticity.","authors":"Maike Hille, Simone Kühn, Gerd Kempermann, Tobias Bonhoeffer, Ulman Lindenberger","doi":"10.1016/j.neuron.2024.10.006","DOIUrl":"10.1016/j.neuron.2024.10.006","url":null,"abstract":"Plasticity allows organisms to form lasting adaptive changes in neural structures in response to interactions with the environment. It serves both species-general functions and individualized skill acquisition. To better understand human plasticity, we need to strengthen the dialogue between human research and animal models. Therefore, we propose to (1) enhance the interpretability of macroscopic methods used in human research by complementing molecular and fine-structural measures used in animals with such macroscopic methods, preferably applied to the same animals, to create macroscopic metrics common to both examined species; (2) launch dedicated cross-species research programs, using either well-controlled experimental paradigms, such as motor skill acquisition, or more naturalistic environments, where individuals of either species are observed in their habitats; and (3) develop conceptual and computational models linking molecular and fine-structural events to phenomena accessible by macroscopic methods. In concert, these three component strategies can foster new insights into the nature of plastic change.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3522-3541"},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A brainstem circuit amplifies aversion. 脑干回路放大了厌恶感。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-12 DOI: 10.1016/j.neuron.2024.08.010

Jingwen Liang, Yu Zhou, Qiru Feng, Youtong Zhou, Tao Jiang, Miao Ren, Xueyan Jia, Hui Gong, Run Di, Peijie Jiao, Minmin Luo

引用次数: 0

Representing the dynamics of natural marmoset vocal behaviors in frontal cortex. 在额叶皮层表现自然狨猴发声行为的动态变化

IF 3.784 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-23 DOI: 10.1016/j.neuron.2024.08.020

Jingwen Li, Mikio C Aoi, Cory T Miller

引用次数: 0

Natural behavior relaxes zoning divisions in the brain. 自然行为会放松大脑中的分区。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.002

Katalin M Gothard, Archer I Bowrie

引用次数: 0

Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition. 人类大脑皮层神经元的突触新生需要物种特异性的 SRGAP2-SYNGAP1 交叉抑制平衡。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-10-14 DOI: 10.1016/j.neuron.2024.08.021

Baptiste Libé-Philippot, Ryohei Iwata, Aleksandra J Recupero, Keimpe Wierda, Sergio Bernal Garcia, Luke Hammond, Anja van Benthem, Ridha Limame, Martyna Ditkowska, Sofie Beckers, Vaiva Gaspariunaite, Eugénie Peze-Heidsieck, Daan Remans, Cécile Charrier, Tom Theys, Franck Polleux, Pierre Vanderhaeghen

{"title":"Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition.","authors":"Baptiste Libé-Philippot, Ryohei Iwata, Aleksandra J Recupero, Keimpe Wierda, Sergio Bernal Garcia, Luke Hammond, Anja van Benthem, Ridha Limame, Martyna Ditkowska, Sofie Beckers, Vaiva Gaspariunaite, Eugénie Peze-Heidsieck, Daan Remans, Cécile Charrier, Tom Theys, Franck Polleux, Pierre Vanderhaeghen","doi":"10.1016/j.neuron.2024.08.021","DOIUrl":"10.1016/j.neuron.2024.08.021","url":null,"abstract":"Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis. SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A,thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments in vivo revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C. Thus, HS genes can modify the phenotypic expression of genetic mutations leading to ID/ASD through the regulation of human synaptic neoteny.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3602-3617.e9"},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gastrointestinal tract cleavage of α-synuclein by asparaginyl endopeptidase leads to Parkinson's disease. 天冬酰胺酰内肽酶通过胃肠道裂解α-突触核蛋白导致帕金森病。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.015

Longfei Li, Valina L Dawson, Ted M Dawson

引用次数: 0

Network-wide risk convergence in gene co-expression identifies reproducible genetic hubs of schizophrenia risk. 基因共表达的全网络风险趋同确定了精神分裂症风险的可重现遗传中心。

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 Epub Date: 2024-09-04 DOI: 10.1016/j.neuron.2024.08.005

Christopher Borcuk, Madhur Parihar, Leonardo Sportelli, Joel E Kleinman, Joo Heon Shin, Thomas M Hyde, Alessandro Bertolino, Daniel R Weinberger, Giulio Pergola

{"title":"Network-wide risk convergence in gene co-expression identifies reproducible genetic hubs of schizophrenia risk.","authors":"Christopher Borcuk, Madhur Parihar, Leonardo Sportelli, Joel E Kleinman, Joo Heon Shin, Thomas M Hyde, Alessandro Bertolino, Daniel R Weinberger, Giulio Pergola","doi":"10.1016/j.neuron.2024.08.005","DOIUrl":"10.1016/j.neuron.2024.08.005","url":null,"abstract":"The omnigenic model posits that genetic risk for traits with complex heritability involves cumulative effects of peripheral genes on mechanistic \"core genes,\" suggesting that in a network of genes, those closer to clusters including core genes should have higher GWAS signals. In gene co-expression networks, we confirmed that GWAS signals accumulate in genes more connected to risk-enriched gene clusters, highlighting across-network risk convergence. This was strongest in adult psychiatric disorders, especially schizophrenia (SCZ), spanning 70% of network genes, suggestive of super-polygenic architecture. In snRNA-seq cell type networks, SCZ risk convergence was strongest in L2/L3 excitatory neurons. We prioritized genes most connected to SCZ-GWAS genes, which showed robust association to a CRISPRa measure of PGC3 regulation and were consistently identified across several brain regions. Several genes, including dopamine-associated ones, were prioritized specifically in the striatum. This strategy thus retrieves current drug targets and can be used to prioritize other potential drug targets.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"3551-3566.e6"},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence. 胶质母细胞瘤功能异质性和肿瘤干细胞富集与肿瘤复发的关系

IF 14.7 1区医学

Neuron Pub Date : 2024-11-06 DOI: 10.1016/j.neuron.2024.10.012

Xuanhua P Xie, Mungunsarnai Ganbold, Jing Li, Michelle Lien, Mollie E Chipman, Tao Wang, Chenura D Jayewickreme, Alicia M Pedraza, Tejus Bale, Viviane Tabar, Cameron Brennan, Daochun Sun, Roshan Sharma, Luis F Parada

{"title":"Glioblastoma functional heterogeneity and enrichment of cancer stem cells with tumor recurrence.","authors":"Xuanhua P Xie, Mungunsarnai Ganbold, Jing Li, Michelle Lien, Mollie E Chipman, Tao Wang, Chenura D Jayewickreme, Alicia M Pedraza, Tejus Bale, Viviane Tabar, Cameron Brennan, Daochun Sun, Roshan Sharma, Luis F Parada","doi":"10.1016/j.neuron.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.neuron.2024.10.012","url":null,"abstract":"Glioblastoma (GBM) is an incurable disease with high intratumoral heterogeneity. Bioinformatic studies have examined transcriptional heterogeneity with differing conclusions. Here, we characterize GBM heterogeneity and highlight critical phenotypic and hierarchical roles for quiescent cancer stem cells (qCSCs). Unsupervised single-cell transcriptomic analysis of patient-derived xenografts (PDXs) delineates six GBM transcriptional states with unique tumor exclusive gene signatures, five of which display congruence with central nervous system (CNS) cell lineages. We employ a surrogate tumor evolution assay by serial xenograft transplantation to demonstrate faithful preservation of somatic mutations, transcriptome, and qCSCs. PDX chemotherapy results in CSC resistance and expansion, also seen in recurrent patient GBM. In aggregate, these novel GBM transcriptional signatures exclusively identify tumor cells and define the hierarchical landscape as stable biologically discernible cell types that allow capture of their evolution upon recurrence, emphasizing the importance of CSCs and demonstrating general relevance to all GBM.","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":14.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0