Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
30
09
2019
accepted:
16
12
2020
pubmed:
27
1
2021
medline:
30
3
2021
entrez:
26
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33495636
doi: 10.1038/s41593-020-00780-7
pii: 10.1038/s41593-020-00780-7
doi:
Substances chimiques
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
355-367Commentaires et corrections
Type : CommentIn
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