Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation
| العنوان: | Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation |
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| المؤلفون: | Lisa Woodworth, Mario Kreutzfeldt, Ingrid Wagner, Fred Wolf, Nellwyn Hagan, Tradite Neziraj, Dimitry Ofengeim, Tanja Jürgens, Joseph Gans, Emily M. Ullrich Gavilanes, Nicolas Snaidero, Thomas Misgeld, Eduardo Beltrán, Juan Daniel Flórez Weidinger, Mehrnoosh Jafari, Adrian-Minh Schumacher, Virág Kocsis-Jutka, Martin Kerschensteiner, Daniel Engels, Ruben Portugues, Doron Merkler, Stephanie S. Schmidt |
| المصدر: | Nature Neuroscience Nature Neuroscience (2021) Nature neuroscience 24(3), 355-367 (2021). doi:10.1038/s41593-020-00780-7 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Dendritic spine, metabolism [Phagocytes], metabolism [Gray Matter], metabolism [Microglia], ddc:616.07, Synapse, Mice, 0302 clinical medicine, pathology [Gray Matter], pathology [Neurons], metabolism [Calcium], Gray Matter, Receptor, Cerebral Cortex, Neurons, metabolism [Inflammation], Phagocytes, Microglia, Chemistry, General Neuroscience, pathology [Multiple Sclerosis], metabolism [Multiple Sclerosis], medicine.anatomical_structure, metabolism [Neurons], medicine.symptom, pathology [Synapses], Multiple Sclerosis, Dendritic Spines, chemistry.chemical_element, Inflammation, Calcium, 03 medical and health sciences, medicine, Animals, ddc:610, Neuroinflammation, pathology [Inflammation], metabolism [Cerebral Cortex], Multiple sclerosis, metabolism [Synapses], medicine.disease, Disease Models, Animal, 030104 developmental biology, metabolism [Dendritic Spines], Synapses, pathology [Cerebral Cortex], pathology [Dendritic Spines], Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Cortical pathology contributes to chronic cognitive impairment of patients suffering from the neuroinflammatory disease multiple sclerosis (MS). How such gray matter inflammation affects neuronal structure and function is not well understood. In the present study, we use functional and structural in vivo imaging in a mouse model of cortical MS to demonstrate that bouts of cortical inflammation disrupt cortical circuit activity coincident with a widespread, but transient, loss of dendritic spines. Spines destined for removal show local calcium accumulations and are subsequently removed by invading macrophages or activated microglia. Targeting phagocyte activation with a new antagonist of the colony-stimulating factor 1 receptor prevents cortical synapse loss. Overall, our study identifies synapse loss as a key pathological feature of inflammatory gray matter lesions that is amenable to immunomodulatory therapy. |
| تدمد: | 1097-6256 |
| DOI: | 10.1038/s41593-020-00780-7 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ebcdb3392cdcf8bf64de6471ae63665 |
| حقوق: | RESTRICTED |
| رقم الأكسشن: | edsair.doi.dedup.....9ebcdb3392cdcf8bf64de6471ae63665 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 10976256 |
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| DOI: | 10.1038/s41593-020-00780-7 |