瑞典卡罗林斯卡学院Bertrand Joseph、Vassilis Stratoulias团队发现表达ARG1的小胶质细胞具有独特的分子特征，并调节出生后小鼠的发育和大脑功能。该研究于2023年5月11日发表于国际学术期刊《自然—神经科学》杂志。

研究人员发现了表达精氨酸酶-1（ARG1;即ARG1+小胶质细胞）的小胶质细胞亚型，该酶主要存在于出生后小鼠早期发育时期的基底前脑和腹侧纹状体中。与ARG1-小胶质细胞相比，ARG1+小胶质细胞富含吞噬细胞内含物，并表现出独特的分子特征，包括Apoe、Clec7a、Igf1、Lgals3和Mgl2等基因表达上调。特异性敲低小胶质细胞中的Arg1会导致胆碱能神经支配不足和胆碱能神经元投射海马体树突棘成熟受损，这反过来又导致雌性小鼠长期的增强缺陷和认知行为受损。该研究结果扩展了小胶质细胞的多样性，并为理解小胶质细胞亚型的特异性功能提供了见解。

据了解，已有报道表明小胶质细胞（CNS中的常驻免疫细胞）的分子多样性。尚未完全阐明以特定蛋白质表达为特征的小胶质细胞亚群是否形成具有不同功能的亚型。

附：英文原文

Title: ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain

Author: Stratoulias, Vassilis, Ruiz, Roco, Kanatani, Shigeaki, Osman, Ahmed M., Keane, Lily, Armengol, Jose A., Rodrguez-Moreno, Antonio, Murgoci, Adriana-Natalia, Garca-Domnguez, Irene, Alonso-Bellido, Isabel, Gonzlez Ibez, Fernando, Picard, Katherine, Vzquez-Cabrera, Guillermo, Posada-Prez, Mercedes, Vernoux, Nathalie, Tejera, Dario, Grabert, Kathleen, Cheray, Mathilde, Gonzlez-Rodrguez, Patricia, Prez-Villegas, Eva M., Martnez-Gallego, Irene, Lastra-Romero, Alejandro, Brodin, David, Avila-Cario, Javier, Cao, Yang, Airavaara, Mikko, Uhln, Per, Heneka, Michael T., Tremblay, Marie-ve, Blomgren, Klas, Venero, Jose L., Joseph, Bertrand

Issue&Volume: 2023-05-11

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.

DOI: 10.1038/s41593-023-01326-3

Source: https://www.nature.com/articles/s41593-023-01326-3