Microglial Extracellular Vesicles as Vehicles for Neurodegeneration Spreading

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.

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases

“…The specific cargo can act locally or be transferred to recipient cells to mediate the functional effects on them [ 83 ]. In the brain, EV have been associated with neuron-glia crosstalk in order to preserve brain homeostasis, although they have also been related to the spreading of certain neurodegenerative diseases [ 84 , 85 ].…”

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

“…Retinal (and brain) microglia also secrete extracellular vesicles (EVs), which are membrane-bound particles composed of mRNA, miRNA, DNA, cytokines, lipids and proteins, regarded as a biopsy of its origin cell [6,38,39]. EVs are involved in cell-to-cell communication by transporting their neuro-protective/toxic components in response to intracellular and extracellular cues as they move through the bloodstream and cerebrospinal fluid (CSF) to reach other cells within close and distant proximity [6,38,39]. EVs include exosomes and ectosomes, which consist of apoptotic bodies and microvesicles [39].…”

“…EVs are involved in cell-to-cell communication by transporting their neuro-protective/toxic components in response to intracellular and extracellular cues as they move through the bloodstream and cerebrospinal fluid (CSF) to reach other cells within close and distant proximity [6,38,39]. EVs include exosomes and ectosomes, which consist of apoptotic bodies and microvesicles [39]. Firstly, many endosomal vesicular bodies fuse to form exosomes (40-160 nm in size) which are then released for intercellular communication [39].…”

“…EVs include exosomes and ectosomes, which consist of apoptotic bodies and microvesicles [39]. Firstly, many endosomal vesicular bodies fuse to form exosomes (40-160 nm in size) which are then released for intercellular communication [39]. Secondly, microvesicles instead originate from the plasma membrane undergoing outward budding (100-1000 nm) [38].…”

“…Finally, apoptotic bodies are >1000 nm in size and form through membrane blebbing of disintegrating, e.g., retinal microglia [38]. In fact, components of apoptotic bodies such as phosphatidyl serine modulate microglial phagocytosis [38,39]. As a result of these diverse features, microglial EVs have recently started to be investigated in relation to neurodegenerative diseases.…”