To properly understand the role microglia play in neurodegeneration, understanding their phenotypes is important. The functional effects of classical activation are geared towards antigen presentation and the killing of intracellular pathogens. Therefore, upregulation of many associated receptors and enzymes reflects that purpose. For example, MHC II, CD86, and Fcγ receptors are upregulated to allow for antigen-presenting activity of microglia and increased crosstalk with other immune cells [19]. In addition, the ratio of particular cytokines has been used to identify inflammatory macrophages and this observation could extend to microglia. For example, since M1 macrophages were found to be a key source of IL-12 [20], it was suggested that IL-12High, IL-10Low production is a simple way to distinguish inflammatory cells [21]. Another potential distinction and an important component of M1 microglia is their ability to produce reactive oxygen species and reactive nitrogen species [22]. A key microglial enzyme associated with this process is inducible nitric oxide synthase (iNOS), which utilizes arginine to produce nitric oxide [23]. However, even though it seems straightforward to identify M1 cells based on these characteristics, classifying these cells in vivo has proven to be more challenging, reflecting the plastic nature of microglia.
