Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing

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dc.creatorYou, Yang
dc.creatorBorgmann, Kathleen
dc.creatorEdara, Venkata Viswanadh
dc.creatorStacy, Satomi
dc.creatorGhorpade, Anuja
dc.creatorIkezu, Tsuneya
dc.creator.orcid0000-0003-0897-390X (Borgmann, Kathleen)
dc.creator.orcid0000-0001-9321-7839 ( Edara, Venkata Viswanadh)
dc.date.accessioned2022-07-12T16:34:45Z
dc.date.available2022-07-12T16:34:45Z
dc.date.issued2019-12-26
dc.description.abstractAstrocytes in the central nervous system (CNS) provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homoeostasis in response to pro-inflammatory factors such as cytokines and pathogen/damage-associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans-cellular communication are still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (ADEVs) under both physiological and pathophysiological conditions. ADEVs were isolated from human primary astrocytes after vehicle (CTL) or interleukin-1beta (IL-1beta) pre-treatment. Label-free quantitative proteomic profiling revealed a notable up-regulation of proteins including actin-associated molecules, integrins and major histocompatibility complex in IL-1beta-ADEVs compared to CTL-ADEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. When fluorescently labelled ADEVs were added into primary cultured mouse cortical neurons, we found a significantly increased neuronal uptake of IL-1beta-ADEVs compared to CTL-ADEVs. We further confirmed it is likely due to the enrichment of surface proteins in IL-1beta-ADEVs, as IL-1beta-ADEVs uptake by neurons was partially suppressed by a specific integrin inhibitor. Additionally, treatment of neurons with IL-1beta-ADEVs also reduced neurite outgrowth, branching and neuronal firing. These findings provide insight for the molecular mechanism of the ADEVs' effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions.
dc.description.sponsorshipThis work is in part funded by Cure Alzheimer's Fund (TI), BrightFocus Foundation (A2016551S), NIH RF1AG054199 (TI), NIH R01AG054672 (TI), NIH R56AG057469 (TI), NIH R21 NS104609 (TI), The Laboratory of Developmental Biology for provided human brain tissues as was support by NIH 5R24 HD0008836 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development.
dc.identifier.citationYou, Y., Borgmann, K., Edara, V. V., Stacy, S., Ghorpade, A., & Ikezu, T. (2019). Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing. Journal of extracellular vesicles, 9(1), 1706801. https://doi.org/10.1080/20013078.2019.1706801
dc.identifier.issn2001-3078
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31577
dc.identifier.volume9
dc.publisherInforma UK Limited, trading as Taylor & Francis Group
dc.relation.urihttps://doi.org/10.1080/20013078.2019.1706801
dc.rights.holderCopyright © 2019 The Author(s).
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceJournal of Extracellular Vesicles
dc.subjectAstrocytes
dc.subjectIL-1beta
dc.subjectexosome
dc.subjectextracellular matrix
dc.subjectextracellular vesicles
dc.subjectinflammatory diseases
dc.subjectneurodegenerative diseases
dc.subjectproteomics
dc.titleActivated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing
dc.typeArticle
dc.type.materialtext

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