Matthew L. Russo, André M. M. Sousa, Anita Bhattacharyya
{"title":"Consequences of trisomy 21 for brain development in Down syndrome","authors":"Matthew L. Russo, André M. M. Sousa, Anita Bhattacharyya","doi":"10.1038/s41583-024-00866-2","DOIUrl":null,"url":null,"abstract":"<p>The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field.</p>","PeriodicalId":19082,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":34.7000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41583-024-00866-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Neuroscience","Score":null,"Total":0}
引用次数: 0
Abstract
The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field.
期刊介绍:
Nature Reviews Neuroscience is a journal that is part of the Nature Reviews portfolio. It focuses on the multidisciplinary science of neuroscience, which aims to provide a complete understanding of the structure and function of the central nervous system. Advances in molecular, developmental, and cognitive neuroscience have made it possible to tackle longstanding neurobiological questions. However, the wealth of knowledge generated by these advancements has created a need for new tools to organize and communicate this information efficiently. Nature Reviews Neuroscience aims to fulfill this need by offering an authoritative, accessible, topical, and engaging resource for scientists interested in all aspects of neuroscience. The journal covers subjects such as cellular and molecular neuroscience, development of the nervous system, sensory and motor systems, behavior, regulatory systems, higher cognition and language, computational neuroscience, and disorders of the brain. Editorial decisions for the journal are made by a team of full-time professional editors who are PhD-level scientists.