Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Paris, France.
Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro, Bari, Italy.
Adv Neurobiol. 2024;37:569-578. doi: 10.1007/978-3-031-55529-9_31.
Microglia are macrophages residing in the central nervous system, where they perform immune surveillance, synaptic remodeling, neurogenesis, and monitor signals arising from brain injuries or potential pathogens.Commonly, rodent models are used for studying microglia because of the available transgenic mouse lines in which specific genetic manipulations are successfully accomplished. However, human and rodents microglia showed significant differences, which are reflected in different morphological and functional properties. These differences are in genetic and transcriptomic, but also in the expression of signaling molecules and age-associated changes.Several strategies are available to study human microglia, as using surgical brain resections from epileptic and tumoral tissues and from post mortem brain samples. In addition, the generation of human-induced pluripotent stem cells (hPSCs) and the possibility to differentiate them in microglia-like cells provide unique opportunities to compare microglia functions between rodents' and human brain.The use of human ex vivo and in vitro brain models allows the study of human microglia, mimicking in vivo conditions. This will be useful for a better understanding of the real live behavior and functions of microglia in the human brain. This chapter aims to highlight significant similarities and differences between human and rodent microglia in order to re-evaluate mouse models of different human brain disorders, proposing the use of in vitro and ex vivo human brain models.Studies on living human microglia in the brain may help to define divergences from animal models and to improve clinical interventions to treat brain pathologies, using alternatives targets.
小胶质细胞是驻留在中枢神经系统中的巨噬细胞,它们在那里执行免疫监视、突触重塑、神经发生,并监测来自脑损伤或潜在病原体的信号。通常,使用啮齿动物模型来研究小胶质细胞,因为有可用的转基因小鼠系,可以成功地进行特定的基因操作。然而,人类和啮齿动物的小胶质细胞存在显著差异,这反映在不同的形态和功能特性上。这些差异存在于遗传和转录组上,但也存在于信号分子的表达和与年龄相关的变化上。有几种策略可用于研究人类小胶质细胞,例如使用来自癫痫和肿瘤组织以及死后脑组织样本的手术脑切除。此外,人类诱导多能干细胞 (hPSC) 的产生和将其分化为小胶质样细胞的可能性为比较啮齿动物和人类大脑中小胶质细胞的功能提供了独特的机会。使用人类离体和体外脑模型可以研究人类小胶质细胞,模拟体内条件。这将有助于更好地理解人类大脑中小胶质细胞的真实行为和功能。本章旨在强调人类和啮齿动物小胶质细胞之间的显著相似性和差异,以重新评估不同人类脑疾病的小鼠模型,并提出使用体外和离体人类脑模型。对大脑中活体人类小胶质细胞的研究可能有助于确定与动物模型的差异,并使用替代靶点改善治疗脑病理学的临床干预措施。