Astrocyte-Derived small extracellular vesicles regulate dendritic complexity through miR-26a-5p activity

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dc.coverageDOI: 10.3390/cells9040930
dc.creatorLuarte, Alejandro
dc.creatorHenzi, Roberto
dc.creatorFernández, Anllely
dc.creatorGaete, Diego
dc.creatorCisternas, Pablo
dc.creatorPizarro, Matias
dc.creatorBatiz, Luis Federico
dc.creatorVillalobos, Isabel
dc.creatorMasalleras, Matias
dc.creatorVergara, Rodrigo
dc.creatorVaras-Godoy, Manuel
dc.creatorAbarzua-Catalan, Lorena
dc.creatorHerrera-Molina, Rodrigo
dc.creatorLafourcade, Carlos
dc.creatorWyneken, Ursula
dc.date2020
dc.date.accessioned2025-11-18T19:47:30Z
dc.date.available2025-11-18T19:47:30Z
dc.description<p>In the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e., GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation, but also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.</p>eng
dc.descriptionIn the last few decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP-tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) that are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e., GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation, but also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/7d82c399-3a69-41f2-9552-45bde429274c
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/55080
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.9 (2020) date: 2020-04-10 nr.4
dc.subjectastrocytes
dc.subjectdendritic complexity
dc.subjectexosomes
dc.subjecthippocampal neurons
dc.subjectmicroRNAs
dc.titleAstrocyte-Derived small extracellular vesicles regulate dendritic complexity through miR-26a-5p activityeng
dc.typeArticleeng
dc.typeArtículospa
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