Abstract
Extracellular vesicles (EVs) play an important role in intercellular communication and are involved in both physiological and pathological processes. In the central nervous system (CNS), EVs secreted from different brain cell types exert a sundry of functions, from modulation of astrocytic proliferation and microglial activation to neuronal protection and regeneration. However, the effect of aging on the biological functions of neural EVs is poorly understood. In this work, we studied the biological effects of small EVs (sEVs) isolated from neural cells maintained for 14 or 21 days in vitro (DIV). We found that EVs isolated from 14 DIV cultures reduced the extracellular levels of lactate dehydrogenase (LDH), the expression levels of the astrocytic protein GFAP, and the complexity of astrocyte architecture suggesting a role in lowering the reactivity of astrocytes, while EVs produced by 21 DIV cells did not show any of the above effects. These results in an in vitro model pave the way to evaluate whether similar results occur in vivo and through what mechanisms.
Highlights
Academic Editor: Fabio CavaliereIn the last years, many studies unveiled the relevant role that extracellular vesicles (EVs) play in intercellular communication, both in physiological processes and in pathological conditions such as cancer, neurodegeneration, or inflammation [1,2,3]
While non-significant differences were found for the expression levels of the microglial marker IBA1 (Figure 6A,B), we found a significant reduction of the glial fibrillary acidic protein (GFAP), an astrocyte-specific marker [23]
We only studied a limited series of biological scenarios, one of them was clearly affected after adding small EVs (sEVs) to the cells: reduced astrocyte reactivity
Summary
Academic Editor: Fabio CavaliereIn the last years, many studies unveiled the relevant role that extracellular vesicles (EVs) play in intercellular communication, both in physiological processes and in pathological conditions such as cancer, neurodegeneration, or inflammation [1,2,3]. EVs are small vesicles secreted by every cell type of the body, consisting of a portion of cytoplasm encapsulated by a lipid bilayer. According to a recent classification based on size, EVs are divided into small EVs (sEV), with a size around 100 nm, and large EVs with sizes ranging from 200 nm to 10 μm [4]. Exosomes originate from the invagination of the limiting membrane of multivesicular bodies (MVBs), a subtype of late-endosomes [5], towards the lumen of the compartment, which gives rise to intraluminal vesicles (ILVs) that contain cytosolic proteins and nucleic acids. MVBs can fuse to lysosomes for degradation of their content or to the plasma membrane, which results in the release of ILVs to the extracellular space in the form of exosomes
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