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Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

Centro de Investigación e Innovación Biomédica (CIIB), Facultad de Medicina, Universidad de los Andes, Santiago 7550000, Chile
Biomedical Neuroscience Institute, Universidad de Chile, Santiago 8380453, Chile
Departamento de Kinesiología, Facultad de Artes y Educación Física, Universidad Metropolitana de Ciencias de la educación, Santiago 7780450, Chile
Cancer Cell Biology Lab, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510157, Chile
Synaptic Signaling Lab, Leibniz İnstitute for Neurobiology; Center for Behavioral Brain Sciences, 39118 Magdeburg, Germany
Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O’Higgins, Santiago 8370993, Chile
Authors to whom correspondence should be addressed.
Cells 2020, 9(4), 930;
Received: 16 February 2020 / Revised: 2 April 2020 / Accepted: 5 April 2020 / Published: 10 April 2020
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. View Full-Text
Keywords: microRNAs; exosomes; astrocytes; hippocampal neurons; dendritic complexity microRNAs; exosomes; astrocytes; hippocampal neurons; dendritic complexity
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Luarte, A.; Henzi, R.; Fernández, A.; Gaete, D.; Cisternas, P.; Pizarro, M.; Batiz, L.F.; Villalobos, I.; Masalleras, M.; Vergara, R.; Varas-Godoy, M.; Abarzua-Catalan, L.; Herrera-Molina, R.; Lafourcade, C.; Wyneken, U. Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity. Cells 2020, 9, 930.

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