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