In particular, recent studies indicate that microglia can modulate neuronal activity, facilitate learning, and shape social behavior. As such, microglia are considered brain-resident macrophages and are uniquely suited to regulate neural homeostasis and behavior. Unlike their fetal liver or bone marrow-derived relatives, microglia arise from embryonic yolk sack progenitors and maintain transcriptional and functional identities distinguishing them from other macrophages which may infiltrate the brain under pathological conditions. Still, microglia are unique among macrophages. Decades later, microglia were recognized as macrophages, evidenced by morphological similarities to peripheral macrophages and their recognition by antisera against common monocyte markers. In the early 1900s, Pío del Río-Hortega described a new type of phagocytic brain cell, of mesodermal origin, that he termed “microglia”.
This approach will enable more precise characterization of microglia in different contexts, which should facilitate development of microglia-directed therapeutics in psychiatric and neurological disease. Further, we propose a framework to better describe changes in microglia1 phenotype and function in chronic stress.
In this review, we summarize primary research on the role of microglia in pathological and physiological contexts. As more studies seek to understand the role of microglia in neurobiology and behavior, it is increasingly important to develop standard methods to study and define microglial phenotype and function. This creates a barrier for investigators new to neuro-immunology and ultimately hinders our understanding of stress effects on microglia. Indeed, terms such as ‘microglia activation’ or ‘neuroinflammation’ are used ubiquitously to describe changes in neuro-immune function in disparate contexts particularly in stress research, where these terms prompt undue comparisons to pathological conditions. Initial reports focused on classical immune functions of microglia in pathological contexts, however, immunological concepts from these studies have been applied to describe neuro-immune interactions in the absence of disease, injury, or infection. Microglia are emerging as critical regulators of neuronal function and behavior in nearly every area of neuroscience.
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