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Down syndrome (DS) is characterized by skeletal and brain structural malformations, cognitive impairment, altered hippocampal metabolite concentration and gene expression imbalance. These alterations were usually investigated separately, and the potential rescuing effects of green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG) provided disparate results due to different experimental conditions. We overcame these limitations by conducting the first longitudinal controlled experiment evaluating genotype and GTE-EGCG prenatal chronic treatment effects before and after treatment discontinuation. Our findings revealed that the Ts65Dn mouse model reflected the pleiotropic nature of DS, exhibiting brachycephalic skull, ventriculomegaly, neurodevelopmental delay, hyperactivity, and impaired memory robustness with altered hippocampal metabolite concentration and gene expression. GTE-EGCG treatment modulated most systems simultaneously but did not rescue DS phenotypes. On the contrary, the treatment exacerbated trisomic phenotypes including body weight, tibia microarchitecture, neurodevelopment, adult cognition, and metabolite concentration, not supporting the therapeutic use of GTE-EGCG as a prenatal chronic treatment. Our results highlight the importance of longitudinal experiments assessing the co-modulation of multiple systems throughout development when characterizing preclinical models in complex disorders and evaluating the pleiotropic effects and general safety of pharmacological treatments.
Pubmed ID: 38497812
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A free, open source software package for visualization and image analysis including registration, segmentation, and quantification of medical image data. Slicer provides a graphical user interface to a powerful set of tools so they can be used by end-user clinicians and researchers alike. 3D Slicer is natively designed to be available on multiple platforms, including Windows, Linux and Mac Os X. Slicer is based on VTK (http://public.kitware.com/vtk) and has a modular architecture for easy addition of new functionality. It uses an XML-based file format called MRML - Medical Reality Markup Language which can be used as an interchange format among medical imaging applications. Slicer is primarily written in C++ and Tcl.
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