Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice

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dc.contributor.authorCarvajal-González, Alexander
dc.contributor.authorJacobson, Leslie W.
dc.contributor.authorClover, Linda M.
dc.contributor.authorWickremaratchi, Mirdhu M.
dc.contributor.authorShields, S.
dc.contributor.authorLang, Bethan
dc.contributor.authorVincent, Angela V.
dc.date.accessioned2020-10-15T22:22:42Z
dc.date.available2020-10-15T22:22:42Z
dc.date.issued2020
dc.description.abstractenglishAims Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a life‐threatening condition often associated with highly raised serum antibodies to glycine receptors (GlyRs); these bind to the surface of large neurons and interneurons in rodent brain and spinal cord sections and, in vitro, inhibit function and reduce surface expression of the GlyRs. The effects in vivo have not been reported. Methods Purified plasma IgG from a GlyR antibody‐positive patient with PERM, and a healthy control (HC), was injected daily into the peritoneal cavity of mice for 12 days; lipopolysaccharide (LPS) to open the blood–brain barrier, was injected on days 3 and 8. Based on preliminary data, behavioural tests were only performed 48 h post‐LPS on days 5–7 and 10–12. Results The GlyR IgG injected mice showed impaired ability on the rotarod from days 5 to 10 but this normalized by day 12. There were no other behavioural differences but, at termination (d13), the GlyR IgG‐injected mice had IgG deposits on the neurons that express GlyRs in the brainstem and spinal cord. The IgG was not only on the surface but also inside these large GlyR expressing neurons, which continued to express surface GlyR. Conclusions Despite the partial clinical phenotype, not uncommon in passive transfer studies, the results suggest that the antibodies had accessed the GlyRs in relevant brain regions, led to antibody‐mediated internalization and increased GlyR synthesis, compatible with the temporary loss of function.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1111/nan.12666
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1365-2990
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/4463
dc.language.isoeng
dc.publisherWiley-Blackwellspa
dc.publisher.journalNeuropathology and applied neurobiologyspa
dc.relation.ispartofseriesNeuropathology and applied neurobiology, 1365-2990, 2020spa
dc.relation.urihttps://onlinelibrary.wiley.com/doi/full/10.1111/nan.12666
dc.rightsAttribution 4.0 International*
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2020-09-10
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.keywordsAnimal modelspa
dc.subject.keywordsAntibody-mediated autoimmune diseasespa
dc.subject.keywordsGlycine receptorspa
dc.subject.keywordsPERMspa
dc.subject.keywordsProgressive encephalomyelitis with rigidity and myoclonusspa
dc.subject.keywordsStiff person syndromespa
dc.titleSystemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in micespa
dc.title.translatedSystemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in micespa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

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