Extracellular Vesicles in the Central Nervous System: A Novel Mechanism of Neuronal Cell Communication

Abstract

Cell-to-cell communication is essential for the appropriate development and maintenance of homeostatic conditions in the central nervous system. Extracellular vesicles have recently come to the forefront of neuroscience as novel vehicles for the transfer of complex signals between neuronal cells. Extracellular vesicles are membrane-bound carriers packed with proteins, metabolites, and nucleic acids (including DNA, mRNA, and microRNAs) that contain the elements present in the cell they originate from. Since their discovery, extracellular vesicles have been studied extensively and have opened up new understanding of cell-cell communication; they may cross the blood-brain barrier in a bidirectional way from the bloodstream to the brain parenchyma and vice versa, and play a key role in brain-periphery communication in physiology as well as pathology. Neurons and glial cells in the central nervous system release extracellular vesicles to the interstitial fluid of the brain and spinal cord parenchyma. Extracellular vesicles contain proteins, nucleic acids, lipids, carbohydrates, and primary and secondary metabolites. that can be taken up by and modulate the behaviour of neighbouring recipient cells. The functions of extracellular vesicles have been extensively studied in the context of neurodegenerative diseases. The purpose of this review is to analyse the role extracellular vesicles extracellular vesicles in central nervous system cell communication, with particular emphasis on the contribution of extracellular vesicles from different central nervous system cell types in maintaining or altering central nervous system homeostasis.

Keywords: astrocytes; central nervous system cells; communication; extracellular vesicle; microglia; oligodendrocytes.

Figure 1

Schematic of the different mechanisms utilized to internalise extracellular vesicles into recipient cells: (A) lipid raft-mediated endocytosis; (B) fusion at the plasma membrane; (C) phagocytosis; (D) clathrin-mediated endocytosis; and (E) interaction with receptors on the plasma membrane.

Figure 2

The figure illustrates the physiological role of extracellular vesicles in the central nervous system. EVs are able to transfer their contents between the different pairs of cell types shown in the figure: astrocytes, neurons, oligodendrocytes, and microglia. The arrows indicate the direction of transfer and are labelled with the content of EVs commonly found for this cell-to-cell communication pathway and some of the functional roles identified for the pathway. Microglial EVs can lead to increased synaptic stability and neuronal synaptic plasticity. Neurons increase glutamate uptake and synaptic pruning. astrocytes release EVs that induce neurite outgrowth. EVs are also derived from oligodendrocytes and contain RNA and protein cargoes that confer neuroprotection to neurons. EVs can also cross the blood–brain barrier (BBB) in both directions to enable communication with peripheral targets.