ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
Date
2023
Authors
Stratoulias, Vassilis
Ruiz, Rocío
Kanatani, Shigeaki
Osman, Ahmed M.
Keane, Lily
Armengol, Jose A.
Rodríguez-Moreno, Antonio
Murgoci, Adriana-Natalia
García-Domínguez, Irene
Alonso-Bellido, Isabel
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Neuroscience
Abstract
Molecular 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.
Description
We would like to thank S. Vazquez and B. Ben-Azu for technical support. We are grateful to P.C. Nahirney for the use of a transmission electron microscope and B. Gowen for technical assistance.
Keywords
Citation
Stratoulias, V., Ruiz, R., Kanatani, S., Osman, A. M., Keane, L., Armengol, J. A., ... Joseph, B. (2023). ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain. Nature Neuroscience, 26, 1008-1020. https://doi.org/10.1038/s41593-023-01326-3