Pub Date : 2024-04-01Epub Date: 2024-03-06DOI: 10.1016/j.tins.2024.02.007
Ming-Han Wang, Yue Hao, Xia-Jing Tong
In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.
{"title":"Targeting the intracellular neurexin interactome by in vivo proximity ligation.","authors":"Ming-Han Wang, Yue Hao, Xia-Jing Tong","doi":"10.1016/j.tins.2024.02.007","DOIUrl":"10.1016/j.tins.2024.02.007","url":null,"abstract":"<p><p>In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060638","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}
Pub Date : 2024-04-01Epub Date: 2024-03-21DOI: 10.1016/j.tins.2024.02.002
Célia Lacaux, Mélanie Strauss, Tristan A Bekinschtein, Delphine Oudiette
Sleep is crucial for many vital functions and has been extensively studied. By contrast, the sleep-onset period (SOP), often portrayed as a mere prelude to sleep, has been largely overlooked and remains poorly characterized. Recent findings, however, have reignited interest in this transitional period and have shed light on its neural mechanisms, cognitive dynamics, and clinical implications. This review synthesizes the existing knowledge about the SOP in humans. We first examine the current definition of the SOP and its limits, and consider the dynamic and complex electrophysiological changes that accompany the descent to sleep. We then describe the interplay between internal and external processing during the wake-to-sleep transition. Finally, we discuss the putative cognitive benefits of the SOP and identify novel directions to better diagnose sleep-onset disorders.
{"title":"Embracing sleep-onset complexity.","authors":"Célia Lacaux, Mélanie Strauss, Tristan A Bekinschtein, Delphine Oudiette","doi":"10.1016/j.tins.2024.02.002","DOIUrl":"10.1016/j.tins.2024.02.002","url":null,"abstract":"<p><p>Sleep is crucial for many vital functions and has been extensively studied. By contrast, the sleep-onset period (SOP), often portrayed as a mere prelude to sleep, has been largely overlooked and remains poorly characterized. Recent findings, however, have reignited interest in this transitional period and have shed light on its neural mechanisms, cognitive dynamics, and clinical implications. This review synthesizes the existing knowledge about the SOP in humans. We first examine the current definition of the SOP and its limits, and consider the dynamic and complex electrophysiological changes that accompany the descent to sleep. We then describe the interplay between internal and external processing during the wake-to-sleep transition. Finally, we discuss the putative cognitive benefits of the SOP and identify novel directions to better diagnose sleep-onset disorders.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190178","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}
Pub Date : 2024-04-01Epub Date: 2024-03-22DOI: 10.1016/j.tins.2024.02.008
Till S Zimmer, Adam L Orr, Anna G Orr
Selective vulnerability of specific brain regions and cell populations is a hallmark of neurodegenerative disorders. Mechanisms of selective vulnerability involve neuronal heterogeneity, functional specializations, and differential sensitivities to stressors and pathogenic factors. In this review we discuss the growing body of literature suggesting that, like neurons, astrocytes are heterogeneous and specialized, respond to and integrate diverse inputs, and induce selective effects on brain function. In disease, astrocytes undergo specific, context-dependent changes that promote different pathogenic trajectories and functional outcomes. We propose that astrocytes contribute to selective vulnerability through maladaptive transitions to context-divergent phenotypes that impair specific brain regions and functions. Further studies on the multifaceted roles of astrocytes in disease may provide new therapeutic approaches to enhance resilience against neurodegenerative disorders.
{"title":"Astrocytes in selective vulnerability to neurodegenerative disease.","authors":"Till S Zimmer, Adam L Orr, Anna G Orr","doi":"10.1016/j.tins.2024.02.008","DOIUrl":"10.1016/j.tins.2024.02.008","url":null,"abstract":"<p><p>Selective vulnerability of specific brain regions and cell populations is a hallmark of neurodegenerative disorders. Mechanisms of selective vulnerability involve neuronal heterogeneity, functional specializations, and differential sensitivities to stressors and pathogenic factors. In this review we discuss the growing body of literature suggesting that, like neurons, astrocytes are heterogeneous and specialized, respond to and integrate diverse inputs, and induce selective effects on brain function. In disease, astrocytes undergo specific, context-dependent changes that promote different pathogenic trajectories and functional outcomes. We propose that astrocytes contribute to selective vulnerability through maladaptive transitions to context-divergent phenotypes that impair specific brain regions and functions. Further studies on the multifaceted roles of astrocytes in disease may provide new therapeutic approaches to enhance resilience against neurodegenerative disorders.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194660","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}
Pub Date : 2024-04-01Epub Date: 2024-02-23DOI: 10.1016/j.tins.2024.01.003
Shahrzad Latifi, S Thomas Carmichael
Stroke is a leading cause of adult disability. Understanding stroke damage and recovery requires deciphering changes in complex brain networks across different spatiotemporal scales. While recent developments in brain readout technologies and progress in complex network modeling have revolutionized current understanding of the effects of stroke on brain networks at a macroscale, reorganization of smaller scale brain networks remains incompletely understood. In this review, we use a conceptual framework of graph theory to define brain networks from nano- to macroscales. Highlighting stroke-related brain connectivity studies at multiple scales, we argue that multiscale connectomics-based approaches may provide new routes to better evaluate brain structural and functional remapping after stroke and during recovery.
{"title":"The emergence of multiscale connectomics-based approaches in stroke recovery.","authors":"Shahrzad Latifi, S Thomas Carmichael","doi":"10.1016/j.tins.2024.01.003","DOIUrl":"10.1016/j.tins.2024.01.003","url":null,"abstract":"<p><p>Stroke is a leading cause of adult disability. Understanding stroke damage and recovery requires deciphering changes in complex brain networks across different spatiotemporal scales. While recent developments in brain readout technologies and progress in complex network modeling have revolutionized current understanding of the effects of stroke on brain networks at a macroscale, reorganization of smaller scale brain networks remains incompletely understood. In this review, we use a conceptual framework of graph theory to define brain networks from nano- to macroscales. Highlighting stroke-related brain connectivity studies at multiple scales, we argue that multiscale connectomics-based approaches may provide new routes to better evaluate brain structural and functional remapping after stroke and during recovery.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944517","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}
Pub Date : 2024-04-01Epub Date: 2024-03-20DOI: 10.1016/j.tins.2024.03.001
Andrii Rudenko, In-Jung Kim
A recent study by Cheung, Pauler, Koppensteiner et al. combining lineage tracing with single-cell RNA sequencing (scRNA-seq) has revealed unexpected features of the developing superior colliculus (SC). Extremely multipotent individual progenitors generate all types of SC neurons and glial cells that were found to localize in a non-predetermined pattern, demonstrating a remarkable degree of unpredictability in SC development.
{"title":"Supermultipotency and unpredictability in the developing superior colliculus.","authors":"Andrii Rudenko, In-Jung Kim","doi":"10.1016/j.tins.2024.03.001","DOIUrl":"10.1016/j.tins.2024.03.001","url":null,"abstract":"<p><p>A recent study by Cheung, Pauler, Koppensteiner et al. combining lineage tracing with single-cell RNA sequencing (scRNA-seq) has revealed unexpected features of the developing superior colliculus (SC). Extremely multipotent individual progenitors generate all types of SC neurons and glial cells that were found to localize in a non-predetermined pattern, demonstrating a remarkable degree of unpredictability in SC development.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11047761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185661","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}
Pub Date : 2024-04-01Epub Date: 2024-03-22DOI: 10.1016/j.tins.2024.03.002
Stephanie Le, Carmen Menacho, Alessandro Prigione
In a recent study, Rylaarsdam and colleagues revealed that mutant PACS1 gene, which causes a rare neurodevelopmental syndrome, affects the firing ability of human neurons without dysregulating the cellular architecture of brain organoids. These findings suggest aberrant neuronal electrophysiology as a possible interventional target for pediatric diseases impairing brain development.
{"title":"Balancing neuronal activity to fight neurodevelopmental disorders.","authors":"Stephanie Le, Carmen Menacho, Alessandro Prigione","doi":"10.1016/j.tins.2024.03.002","DOIUrl":"10.1016/j.tins.2024.03.002","url":null,"abstract":"<p><p>In a recent study, Rylaarsdam and colleagues revealed that mutant PACS1 gene, which causes a rare neurodevelopmental syndrome, affects the firing ability of human neurons without dysregulating the cellular architecture of brain organoids. These findings suggest aberrant neuronal electrophysiology as a possible interventional target for pediatric diseases impairing brain development.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194661","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}
Pub Date : 2024-04-01Epub Date: 2024-03-19DOI: 10.1016/j.tins.2024.02.001
Sebastian Dohm-Hansen, Jane A English, Aonghus Lavelle, Carlos P Fitzsimons, Paul J Lucassen, Yvonne M Nolan
Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan.
{"title":"The 'middle-aging' brain.","authors":"Sebastian Dohm-Hansen, Jane A English, Aonghus Lavelle, Carlos P Fitzsimons, Paul J Lucassen, Yvonne M Nolan","doi":"10.1016/j.tins.2024.02.001","DOIUrl":"10.1016/j.tins.2024.02.001","url":null,"abstract":"<p><p>Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140176687","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}
Pub Date : 2024-04-01Epub Date: 2024-03-13DOI: 10.1016/j.tins.2024.02.005
Albrecht Stroh, Susann Schweiger, Jan-Marino Ramirez, Oliver Tüscher
Neuronal networks possess the ability to regulate their activity states in response to disruptions. How and when neuronal networks turn from physiological into pathological states, leading to the manifestation of neuropsychiatric disorders, remains largely unknown. Here, we propose that neuronal networks intrinsically maintain network stability even at the cost of neuronal loss. Despite the new stable state being potentially maladaptive, neural networks may not reverse back to states associated with better long-term outcomes. These maladaptive states are often associated with hyperactive neurons, marking the starting point for activity-dependent neurodegeneration. Transitions between network states may occur rapidly, and in discrete steps rather than continuously, particularly in neurodegenerative disorders. The self-stabilizing, metastable, and noncontinuous characteristics of these network states can be mathematically described as attractors. Maladaptive attractors may represent a distinct pathophysiological entity that could serve as a target for new therapies and for fostering resilience.
{"title":"The selfish network: how the brain preserves behavioral function through shifts in neuronal network state.","authors":"Albrecht Stroh, Susann Schweiger, Jan-Marino Ramirez, Oliver Tüscher","doi":"10.1016/j.tins.2024.02.005","DOIUrl":"10.1016/j.tins.2024.02.005","url":null,"abstract":"<p><p>Neuronal networks possess the ability to regulate their activity states in response to disruptions. How and when neuronal networks turn from physiological into pathological states, leading to the manifestation of neuropsychiatric disorders, remains largely unknown. Here, we propose that neuronal networks intrinsically maintain network stability even at the cost of neuronal loss. Despite the new stable state being potentially maladaptive, neural networks may not reverse back to states associated with better long-term outcomes. These maladaptive states are often associated with hyperactive neurons, marking the starting point for activity-dependent neurodegeneration. Transitions between network states may occur rapidly, and in discrete steps rather than continuously, particularly in neurodegenerative disorders. The self-stabilizing, metastable, and noncontinuous characteristics of these network states can be mathematically described as attractors. Maladaptive attractors may represent a distinct pathophysiological entity that could serve as a target for new therapies and for fostering resilience.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132635","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}
Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies (LBs). The main proteinaceous component of LBs is aggregated α-synuclein (α-syn). However, the mechanisms underlying α-syn aggregation are not yet fully understood. Converging lines of evidence indicate that, under certain pathological conditions, various proteins can interact with α-syn and regulate its aggregation. Understanding these protein-protein interactions is crucial for unraveling the molecular mechanisms contributing to PD pathogenesis. In this review we provide an overview of the current knowledge on protein-protein interactions that regulate α-syn aggregation. Additionally, we briefly summarize the methods used to investigate the influence of protein-protein interactions on α-syn aggregation and propagation.
帕金森病(Parkinson's disease,PD)是一种神经退行性疾病,其特征是黑质上皮(substantia nigra pars compacta,SNpc)中的多巴胺能神经元变性并形成路易体(Lewy bodies,LBs)。路易体的主要蛋白成分是聚集的α-突触核蛋白(α-syn)。然而,α-syn聚集的机制尚未完全明了。越来越多的证据表明,在某些病理条件下,各种蛋白质可与α-syn相互作用并调节其聚集。了解这些蛋白质之间的相互作用对于揭示导致帕金森病发病的分子机制至关重要。在这篇综述中,我们概述了目前有关调控α-syn聚集的蛋白-蛋白相互作用的知识。此外,我们还简要总结了用于研究蛋白-蛋白相互作用对α-syn聚集和传播的影响的方法。
{"title":"Protein-protein interactions regulating α-synuclein pathology.","authors":"Jiannan Wang, Lijun Dai, Sichun Chen, Zhaohui Zhang, Xin Fang, Zhentao Zhang","doi":"10.1016/j.tins.2024.01.002","DOIUrl":"10.1016/j.tins.2024.01.002","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation of Lewy bodies (LBs). The main proteinaceous component of LBs is aggregated α-synuclein (α-syn). However, the mechanisms underlying α-syn aggregation are not yet fully understood. Converging lines of evidence indicate that, under certain pathological conditions, various proteins can interact with α-syn and regulate its aggregation. Understanding these protein-protein interactions is crucial for unraveling the molecular mechanisms contributing to PD pathogenesis. In this review we provide an overview of the current knowledge on protein-protein interactions that regulate α-syn aggregation. Additionally, we briefly summarize the methods used to investigate the influence of protein-protein interactions on α-syn aggregation and propagation.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736217","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}
Pub Date : 2024-03-01Epub Date: 2024-02-19DOI: 10.1016/j.tins.2024.02.004
Yue Hao, Kang-Ying Qian, Qian Li
In a recent study, Pourmorady and colleagues uncovered a noncoding role for olfactory receptor (OR)-coding mRNA in mediating nuclear architecture and singular OR choice. The OR mRNAs reinforce the prevailing enhancer hub and inhibit other competitors, facilitating transition from polygenic to singular OR expression.
在最近的一项研究中,Pourmorady 及其同事发现了嗅觉受体(OR)编码 mRNA 在介导核结构和单一 OR 选择方面的非编码作用。嗅觉受体编码 mRNA 强化了主要的增强子枢纽,抑制了其他竞争者,促进了从多基因到单一嗅觉受体表达的过渡。
{"title":"A noncoding role of coding mRNA in monogenic olfactory receptor choice.","authors":"Yue Hao, Kang-Ying Qian, Qian Li","doi":"10.1016/j.tins.2024.02.004","DOIUrl":"10.1016/j.tins.2024.02.004","url":null,"abstract":"<p><p>In a recent study, Pourmorady and colleagues uncovered a noncoding role for olfactory receptor (OR)-coding mRNA in mediating nuclear architecture and singular OR choice. The OR mRNAs reinforce the prevailing enhancer hub and inhibit other competitors, facilitating transition from polygenic to singular OR expression.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":15.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913574","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}