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Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance. In contrast, process outgrowth to damaged tissue requires P2Y12 receptor activation but is unaffected by blocking THIK-1. Block of THIK-1 function also inhibits release of the pro-inflammatory cytokine interleukin-1β from activated microglia, consistent with K+ loss being needed for inflammasome assembly. Thus, microglial immune surveillance and cytokine release require THIK-1 channel activity.
Pubmed ID: 29290552
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Center that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsA handy, fast, and versatile 3D/4D/5D Image Visualization & Analysis System for Bioimages & Surface Objects. Vaa3D is a cross-platform (Mac, Linux, and Windows) tool for visualizing large-scale (gigabytes, and 64-bit data) 3D/4D/5D image stacks and various surface data. It is also a container of powerful modules for 3D image analysis (cell segmentation, neuron tracing, brain registration, annotation, quantitative measurement and statistics, etc) and data management. Vaa3D is very easy to be extended via a powerful plugin interface. For example, many ITK tools are being converted to Vaa3D Plugins. Vaa3D-Neuron is built upon Vaa3D to make 3D neuron reconstruction much easier. In a recent Nature Biotechnology paper (2010, 28(4), pp.348-353) about Vaa3D and Vaa3D-Neuron, an order of magnitude of performance improvement (both reconstruction accuracy and speed) was achieved compared to other tools.
View all literature mentionsAn Antibody supplier; Dako was purchased by Agilent in 2012 and several years later the websites began to reflect the Dako products as part of the Agilent catalog.
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