Equipped with highly ramified and motile processes extending from a compact cell body, microglia are constantly surveying their brain microenvironment (Nimmerjahn et al., 2005; Ohsawa and Kohsaka, 2011). Microglia detect foreign pathogens or danger signals in the CNS directly through PPRs (such as TLRs) and, indirectly, through cytokine and chemokine receptors (such as IL-1R or TNFR) (Streit, 2002). When microglia sense these threats, they become “activated”. The classical view of microglia activation consists of a morphological transformation from a ramified phenotype to an amoeboid, phagocytic, macrophage-like cell. This transformation is visualized by increased size of cell bodies, decreased length of processes, and increased immunoreactivity of ionized calcium-binder adapter molecule 1 (IBA1, a calcium binding protein found in microglia and macrophages). Microglia have traditionally been thought to form two distinct activation profiles, M1 and M2, each having opposing effects on inflammation (Tang and Le, 2016). M1 microglia secrete pro-inflammatory molecules (TNF-α, IL-1β, and IL-6) while M2 microglia release anti-inflammatory molecules (TGF-β and IL-10). However, unbiased global analysis techniques, such as whole-genome transcriptome analysis, indicate that microglia activation is more complex than
