Neuroprotective and Neurotoxic Effects of Glial-Derived Exosomes

Abstract

Exosomes derived from glial cells such as astrocytes, microglia, and oligodendrocytes can modulate cell communication in the brain and exert protective or neurotoxic effects on neurons, depending on the environmental context upon their release. Their isolation, characterization, and analysis under different conditions in vitro, in animal models and samples derived from patients has allowed to define the participation of other molecular mechanisms behind neuroinflammation and neurodegeneration spreading, and to propose their use as a potential diagnostic tool. Moreover, the discovery of specific molecular cargos, such as cytokines, membrane-bound and soluble proteins (neurotrophic factors, growth factors, misfolded proteins), miRNA and long-non-coding RNA, that are enriched in glial-derived exosomes with neuroprotective or damaging effects, or their inhibitors can now be tested as therapeutic tools. In this review we summarize the state of the art on how exosomes secretion by glia can affect neurons and other glia from the central nervous system in the context of neurodegeneration and neuroinflammation, but also, on how specific stress stimuli and pathological conditions can change the levels of exosome secretion and their properties.

Keywords: astrocytes; exosomes; microglia; neuroinflammation; neuroprotective; neurotoxic; oligodendrocyte.

FIGURE 1

Glial-derived exosomes isolation strategies from blood or plasma. Extracellular vesicles (EVs) are released by glial cells, containing different cargo molecules such as cytokines, proteins, and non-coding RNA. The ability of EVs to cross the blood–brain barrier (BBB), allows them to enter the peripheral blood and cerebrospinal fluid (CSF). Isolation of glial cell-derived exosomes from blood or CSF is accomplished by identifying glial-specific proteins surface markers, such as glutamate aspartate transporter (GLAST) for astrocytes, CD11b and isolectin B4 (IB4) for microglia, and oligodendrocyte-myelin glycoprotein (OMG) for oligodendrocytes.

FIGURE 2

Glial cells-derived exosomes coposition and their participation in neuroprotective, neurotoxic, and regulatory functions. Summary of the information reported about the cargo of exosomes derived from glial cells and their effects observed in different physiological and pathophysiological models in vitro and in vivo.