Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.
Neurodegenerative Disease Research Center and School of Life Sciences, Arizona State University, Tempe, AZ 84027, USA.
Cells. 2019 Aug 5;8(8):838. doi: 10.3390/cells8080838.
Experimental studies of neuroinflammation in Alzheimer's disease (AD) have mostly investigated microglia, the brain-resident macrophages. This review focused on human microglia obtained at rapid autopsies. Studies employing methods to isolate and culture human brain microglia in high purity for experimental studies were discussed. These methods were employed to isolate human microglia for investigation of a number of features of neuroinflammation, including activation phenotypes, neurotoxicity, responses to abnormal aggregated proteins such as amyloid beta, phagocytosis, and the effects of aging and disease on microglia cellular properties. In recent years, interest in human microglia and neuroinflammation has been renewed due to the identification of inflammation-related AD genetic risk factors, in particular the triggering receptor expressed on myeloid cells (TREM)-2. Because of the difficulties in developing effective treatments for AD, there has been a general need for greater understanding of the functions of microglia in normal and AD brains. While most experimental studies on neuroinflammation have employed rodent microglia, this review considered the role of human microglia in experimental studies. This review focused on the development of in vitro methodology for the culture of postmortem human microglia and the key findings obtained from experimental studies with these cells.
阿尔茨海默病(AD)神经炎症的实验研究大多集中在小胶质细胞上,即大脑驻留的巨噬细胞。本综述聚焦于快速尸检获得的人小胶质细胞。本文讨论了用于分离和培养高纯度人脑小胶质细胞进行实验研究的方法。这些方法被用于分离人小胶质细胞,以研究神经炎症的许多特征,包括激活表型、神经毒性、对异常聚集蛋白(如β淀粉样蛋白)的反应、吞噬作用以及衰老和疾病对小胶质细胞细胞特性的影响。近年来,由于鉴定出与炎症相关的 AD 遗传风险因素,特别是髓样细胞表达的触发受体 2(TREM-2),人们对人小胶质细胞和神经炎症的兴趣重新燃起。由于 AD 治疗方法的开发存在困难,因此人们普遍需要更深入地了解小胶质细胞在正常和 AD 大脑中的功能。虽然大多数神经炎症的实验研究都采用了啮齿动物小胶质细胞,但本综述考虑了人小胶质细胞在实验研究中的作用。本综述重点介绍了培养死后人类小胶质细胞的体外方法学的发展,以及这些细胞的实验研究中获得的关键发现。