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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.
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http://dx.doi.org/10.1038/s41583-024-00866-2 | DOI Listing |
J Magn Reson Imaging
September 2025
Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, Texas, USA.
Background: Cerebrovascular reactivity reflects changes in cerebral blood flow in response to an acute stimulus and is reflective of the brain's ability to match blood flow to demand. Functional MRI with a breath-hold task can be used to elicit this vasoactive response, but data validity hinges on subject compliance. Determining breath-hold compliance often requires external monitoring equipment.
View Article and Find Full Text PDFHum Brain Mapp
September 2025
Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Perinatal stroke is a vascular injury occurring early in life, often resulting in motor deficits (hemiplegic cerebral palsy/HCP). Comorbidities may also include poor neuropsychological outcomes, such as deficits in memory. Previous studies have used resting state functional MRI (fMRI) to demonstrate that functional connectivity (FC) within hippocampal circuits is associated with memory function in typically developing controls (TDC) and in adults after stroke, but this is unexplored in perinatal stroke.
View Article and Find Full Text PDFHum Brain Mapp
September 2025
Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany.
Acting intentionally is a major aspect of human cognitive development and depends on the ability to link actions with their consequences. Action-effect binding (AEB) is a fundamental mechanism enabling this. While AEB has been well-characterized in adults, its neurophysiological underpinnings during adolescence remain unclear.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Scool of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072.
Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear.
View Article and Find Full Text PDFEur J Heart Fail
September 2025
School of Cardiovascular & Metabolic Medicine and Science, James Black Centre, King's College London British Heart Foundation Centre of Excellence, London, UK.
Aims: Skeletal muscle energetic augmentation might be a mechanism via which intravenous iron improves symptoms in heart failure, but no direct measurement of intrinsic mitochondrial function has been performed to support this notion. This molecular substudy of the FERRIC-HF II trial tested the hypothesis that ferric derisomaltose (FDI) would improve electron transport chain activity, given its high dependence on iron-sulfur clusters which facilitate electron transfer during oxidative phosphorylation.
Methods And Results: Vastus lateralis skeletal muscle biopsies were taken before and 2 weeks after randomization.