4 MICROGLIAL ORIGINS AND ACTIVATED PHENOTYPES
Although microglia develop within a unique environment compared to other immune cells, activated microglia are frequently referred to as ‘brain macrophages’, and they share many similarities with macrophages resident in peripheral (non-CNS) tissues. Early histological observations noted that microglia could exhibit ramified or amoeboid morphologies. Recently, a wider variety of phenotypes have been described, based on markers and behaviours similar to those of macrophages. This has lead to the adoption of similar nomenclature for both. The unactivated (default) microglial phenotype, present throughout the ‘healthy’ CNS, is often described as ‘resting’. However, this term fails to reflect the high levels of activity displayed by these cells, which actively survey their local microenvironment using highly motile processes. Here, this phenotype will be termed M0, with the activated phenotypes being referred to as M1 (also known as ‘classically…show more content… Microglial activation can produce numerous and varied consequences. The white box indicates events, which can cause microglial activation. Activated microglia can adopt several phenotypes, and these may lead to adverse effects on other neural cells (e.g. red-bordered boxes) or protective effects (e.g. green-bordered box). Adapted from. 16
A number of markers have been reported for the identification of microglia, but it has become apparent that more detailed analyses are required. As different microglial phenotypes can perform very different functions, a useful assessment requires identification of specific microglial phenotypes. Unactivated (M0) microglia have few unambiguous markers/hallmarks. Activated microglia have been classified broadly into M1 and M2 phenotypes, but a number of M2 subtypes have also been proposed, based on a wide variety of markers (Table 1). There is considerable research devoted to establishing which markers most reliably identify each