Abstract
Microglial cells are the neuroimmune competent cells of the central nervous system. In the adult, microglia are responsible for screening the neuronal parenchyma searching for alterations in homeostasis. Chronic neuroinflammation plays a role in neurodegenerative disease. Indeed, microglia-mediated neuroinflammation is involved in the onset and progression of several disorders in the brain and retina. Microglial cell reactivity occurs in an orchestrated manner and propagates across the neural parenchyma spreading the neuroinflammatory signal from cell to cell. Extracellular vesicles are important vehicles of intercellular communication and act as message carriers across boundaries. Extracellular vesicles can be subdivided in several categories according to their cellular origin (apoptotic bodies, microvesicles and exosomes), each presenting, different but sometimes overlapping functions in cell communication. Mounting evidence suggests a role for extracellular vesicles in regulating microglial cell action. Herein, we explore the role of microglial extracellular vesicles as vehicles for cell communication and the mechanisms that trigger their release. In this review we covered the role of microglial extracellular vesicles, focusing on apoptotic bodies, microvesicles and exosomes, in the context of neurodegeneration and the impact of these vesicles derived from other cells in microglial cell reactivity.
Highlights
Microglial cells are the main neuroimmune cells of the central nervous system (CNS)that comprise 5–12% of the cells in brain [1] and 0.2% of total retinal cells [2]
Opposite to what was described above for microvesicles derived from microglia isolated from Traumatic brain injury (TBI) brains, exposure of microglial cells to neuronal extracts from TBI brains lead to the release of anti-inflammatory and neurotrophic exosomes enriched in miR-124-3p, from microglia in vitro promoting neurite outgrowth [207]
In the beginning regarded as cell waste materials, extracellular vesicles (EVs) were later viewed as a mirror of the cell status, but more recently evidence demonstrate that cargo is selectively loaded into EVs, acting as message carriers [213]
Summary
Microglial cells are the main neuroimmune cells of the central nervous system (CNS). that comprise 5–12% of the cells in brain [1] and 0.2% of total retinal cells [2]. (ii) physiological housekeeping function that includes synaptic remodeling and migration to sites of neuronal death to phagocyte dead cells and (iii) protection against detrimental agents (reviewed in [3]). Despite their role on the maintenance of homeostasis, microglia are deeply involved in neuroinflammation, since a sustained response of microglia can have deleterious effects. Microglia become highly mobile, decrease in size, retract their processes and release a plethora of factors that include inflammatory cytokines, chemokines and reactive oxygen species [3,4,5] Together with all these soluble factors microglia secrete extracellular vesicles (EVs) [6], which are involved in intercellular communication. The distinction between microvesicles and exosomes was made based on the isolation methods and identification described in the original studies
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