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Catching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca2+ imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington's disease pathogenesis long before the onset of clinical symptoms.
Pubmed ID: 30179155 RIS Download
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Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
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View all literature mentionsMus musculus with name B6.129P2-Htttm2Detl/150J from IMSR.
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsVideo tracking software that tracks and analyzes the behavior, movement, and activity of any animal.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsSoftware toolkit for data aquisition and analysis. Its features include remote control of Abberior Instruments microscopes via a Python/MATLAB script, third-party compatibility with other data-analysis softwares/methods, and the easyCommander graphical user interface for experimental set up.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsSoftware used for visualizing and graphing data, image processing, and programming. It is designed for use by scientists and engineers and supports large data sets, evenly spaced data, and various data import formats. The software includes a suite of image processing operations for image filtering, manipulation, and quantification and is completely programmable.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis unknown targets Donkey Serum
View all literature mentionsThis unknown targets Rabbit IgG, F'2 Fragment Specific
View all literature mentionsThis unknown targets Mouse IgG, F'2 Fragment Specific
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis polyclonal targets Actin
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets Huntingtin antibody [EPR5526]
View all literature mentionsThis polyclonal targets GFAP
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsCaenorhabditis elegans with name rmIs133 [unc-54p::Q40::YFP]X from WB.
View all literature mentionsMus musculus with name B6.129P2-Htttm2Detl/150J from IMSR.
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets NORMAL SHEEP SERUM
View all literature mentionsThis unknown targets NORMAL SHEEP SERUM
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsCell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name B6.129P2-Htttm2Detl/150J from IMSR.
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