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dc.contributor.authorSalvany, Sara
dc.contributor.authorCasanovas i Llorens, Anna
dc.contributor.authorPiedrafita Llorens, Lídia
dc.contributor.authorTarabal Mostazo, Olga
dc.contributor.authorHernández, Sara
dc.contributor.authorCalderó i Pardo, Jordi
dc.contributor.authorEsquerda Colell, Josep
dc.date.accessioned2021-02-19T09:24:06Z
dc.date.available2021-02-19T09:24:06Z
dc.date.issued2021-01-02
dc.identifier.issn0894-1491
dc.identifier.urihttp://hdl.handle.net/10459.1/70556
dc.description.abstractPeripheral nerve section with subsequent disconnection of motor neuron (MN) cell bodies from their skeletal muscle targets leads to a rapid reactive response involving the recruitment and activation of microglia. In addition, the loss of afferent synapses on MNs occurs in concomitance with microglial reaction by a process described as synaptic stripping. However, the way in which postaxotomy‐activated microglia adjacent to MNs are involved in synaptic removal is less defined. Here, we used confocal and electron microscopy to examine interactions between recruited microglial cells and presynaptic terminals in axotomized MNs between 1 and 15 days after sciatic nerve transection in mice. We did not observe any bulk engulfment of synaptic boutons by microglia. Instead, microglial cells internalized small membranous‐vesicular fragments which originated from the acute disruption of synaptic terminals involving the activation of the necroptotic pathway. The presence of abundant extracellular vesicles in the perineuronal space after axotomy, together with the increased expression of phospho‐mixed lineage kinase domain‐like protein and, later, of extracellular vesicle markers, such as CD9, CD63, and flotillin, indicate that the vesicles mainly originated in synapses and were transferred to microglia. The upregulation of Rab7 and Rab10 in microglia interacting with injured MNs, indicated the activation of endocytosis. As activated microglia and synaptic boutons displayed positive C1q immunoreactivity, a complement‐mediated opsonization may also contribute to microglial‐mediated synaptic disruption. In addition to the relevance of our data in the context of neuroinflammation and MN disease, they should also be taken into account for understanding functional recovery after peripheral nerve injury.
dc.description.sponsorshipMinisterio de Ciencia, Innovación y Universidades (MICIU) and Fondo Europeo de Desarrollo Regional (FEDER), Grant/Award Number: RTI2018-099278-B-I00; Spanish Ministerio de Educación, Cultura y Deporte; Jack Van den Hock a la Investigació de l'ELA - Fundació Miquel Valls
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherWiley
dc.relationMINECO/PN20107-2020/RTI2018-099278-B-I00
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1002/glia.23959
dc.relation.ispartofGlia, 2021, vol. In press
dc.rightscc-by-nc-nd (c) Salvany et al., 2021
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAfferent synapses
dc.subjectExtracellular vesicles
dc.subjectExosomes
dc.subjectMicroglia
dc.subjectMotor neuron
dc.subjectNerve axotomy
dc.subjectNecroptosis
dc.titleMicroglial recruitment and mechanisms involved in the disruption of afferent synaptic terminals on spinal cord motor neurons after acute peripheral nerve injury
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2021-02-19T09:24:06Z
dc.identifier.idgrec030677
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1002/glia.23959


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cc-by-nc-nd (c) Salvany et al., 2021
Except where otherwise noted, this item's license is described as cc-by-nc-nd (c) Salvany et al., 2021