TY - JOUR
T1 - Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation
AU - Jafari, Mehrnoosh
AU - Schumacher, Adrian Minh
AU - Snaidero, Nicolas
AU - Ullrich Gavilanes, Emily M.
AU - Neziraj, Tradite
AU - Kocsis-Jutka, Virág
AU - Engels, Daniel
AU - Jürgens, Tanja
AU - Wagner, Ingrid
AU - Weidinger, Juan Daniel Flórez
AU - Schmidt, Stephanie S.
AU - Beltrán, Eduardo
AU - Hagan, Nellwyn
AU - Woodworth, Lisa
AU - Ofengeim, Dimitry
AU - Gans, Joseph
AU - Wolf, Fred
AU - Kreutzfeldt, Mario
AU - Portugues, Ruben
AU - Merkler, Doron
AU - Misgeld, Thomas
AU - Kerschensteiner, Martin
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85099847846&partnerID=8YFLogxK
U2 - 10.1038/s41593-020-00780-7
DO - 10.1038/s41593-020-00780-7
M3 - Article
C2 - 33495636
AN - SCOPUS:85099847846
SN - 1097-6256
VL - 24
SP - 355
EP - 367
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 3
ER -