Abstract
AbstractMolecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1– microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
Funder
Sigrid Juséliuksen Säätiö
Svenska Kulturfonden
Academy of Finland
Barncancerfonden
Spanish Ministerio de Ciencia e Innovación
Mexican Council of Science and Technology
Wenner-Gren Foundation
Cancerfonden
Åke Wiberg Stiftelse
ERA-NET NEURON Neuroinflammation
Fonds de Recherche du Québec - Santé
ERA-NET NEURON Neuroinflammation Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition
Swedish governmental grants for researchers working in healthcare
Spanish Ministerio de Ciencia e Innovación Spanish Junta de Andalucia
Vetenskapsrådet
Hjärnfonden
Radiumhemmets Forskningsfonder
Karolinska Institutet
Publisher
Springer Science and Business Media LLC
Cited by
9 articles.
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