| Literature DB >> 33495636 |
Mehrnoosh Jafari1,2, Adrian-Minh Schumacher1,2, Nicolas Snaidero1,3,4, Emily M Ullrich Gavilanes1,2, Tradite Neziraj1,2, Virág Kocsis-Jutka1,2, Daniel Engels1,2, Tanja Jürgens5, Ingrid Wagner5, Juan Daniel Flórez Weidinger6,7,8,9, Stephanie S Schmidt1, Eduardo Beltrán1,2, Nellwyn Hagan10, Lisa Woodworth10, Dimitry Ofengeim10, Joseph Gans11, Fred Wolf6,7,8,9,12, Mario Kreutzfeldt5,13, Ruben Portugues14,15, Doron Merkler16,17, Thomas Misgeld18,19,20, Martin Kerschensteiner21,22,23.
Abstract
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.Entities:
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Year: 2021 PMID： 33495636 DOI： 10.1038/s41593-020-00780-7
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884