Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice
Aims 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,...
- Autores:
-
Carvajal-González, Alexander
Jacobson, Leslie W.
Clover, Linda M.
Wickremaratchi, Mirdhu M.
Shields, S.
Lang, Bethan
Vincent, Angela V.
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2020
- Institución:
- Universidad El Bosque
- Repositorio:
- Repositorio U. El Bosque
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unbosque.edu.co:20.500.12495/4463
- Acceso en línea:
- http://hdl.handle.net/20.500.12495/4463
https://doi.org/10.1111/nan.12666
- Palabra clave:
- Animal model
Antibody-mediated autoimmune disease
Glycine receptor
PERM
Progressive encephalomyelitis with rigidity and myoclonus
Stiff person syndrome
- Rights
- openAccess
- License
- Attribution 4.0 International
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dc.title.spa.fl_str_mv |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
dc.title.translated.spa.fl_str_mv |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
title |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
spellingShingle |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice Animal model Antibody-mediated autoimmune disease Glycine receptor PERM Progressive encephalomyelitis with rigidity and myoclonus Stiff person syndrome |
title_short |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
title_full |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
title_fullStr |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
title_full_unstemmed |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
title_sort |
Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
dc.creator.fl_str_mv |
Carvajal-González, Alexander Jacobson, Leslie W. Clover, Linda M. Wickremaratchi, Mirdhu M. Shields, S. Lang, Bethan Vincent, Angela V. |
dc.contributor.author.none.fl_str_mv |
Carvajal-González, Alexander Jacobson, Leslie W. Clover, Linda M. Wickremaratchi, Mirdhu M. Shields, S. Lang, Bethan Vincent, Angela V. |
dc.subject.keywords.spa.fl_str_mv |
Animal model Antibody-mediated autoimmune disease Glycine receptor PERM Progressive encephalomyelitis with rigidity and myoclonus Stiff person syndrome |
topic |
Animal model Antibody-mediated autoimmune disease Glycine receptor PERM Progressive encephalomyelitis with rigidity and myoclonus Stiff person syndrome |
description |
Aims 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. |
publishDate |
2020 |
dc.date.accessioned.none.fl_str_mv |
2020-10-15T22:22:42Z |
dc.date.available.none.fl_str_mv |
2020-10-15T22:22:42Z |
dc.date.issued.none.fl_str_mv |
2020 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.local.none.fl_str_mv |
Artículo de revista |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
format |
http://purl.org/coar/resource_type/c_6501 |
dc.identifier.issn.none.fl_str_mv |
1365-2990 |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/20.500.12495/4463 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1111/nan.12666 |
dc.identifier.instname.spa.fl_str_mv |
instname:Universidad El Bosque |
dc.identifier.reponame.spa.fl_str_mv |
reponame:Repositorio Institucional Universidad El Bosque |
dc.identifier.repourl.none.fl_str_mv |
repourl:https://repositorio.unbosque.edu.co |
identifier_str_mv |
1365-2990 instname:Universidad El Bosque reponame:Repositorio Institucional Universidad El Bosque repourl:https://repositorio.unbosque.edu.co |
url |
http://hdl.handle.net/20.500.12495/4463 https://doi.org/10.1111/nan.12666 |
dc.language.iso.none.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofseries.spa.fl_str_mv |
Neuropathology and applied neurobiology, 1365-2990, 2020 |
dc.relation.uri.none.fl_str_mv |
https://onlinelibrary.wiley.com/doi/full/10.1111/nan.12666 |
dc.rights.*.fl_str_mv |
Attribution 4.0 International |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
dc.rights.local.spa.fl_str_mv |
Acceso abierto |
dc.rights.accessrights.none.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess Acceso abierto |
dc.rights.creativecommons.none.fl_str_mv |
2020-09-10 |
rights_invalid_str_mv |
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ Acceso abierto http://purl.org/coar/access_right/c_abf2 2020-09-10 |
eu_rights_str_mv |
openAccess |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
Wiley-Blackwell |
dc.publisher.journal.spa.fl_str_mv |
Neuropathology and applied neurobiology |
institution |
Universidad El Bosque |
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Carvajal-González, AlexanderJacobson, Leslie W.Clover, Linda M.Wickremaratchi, Mirdhu M.Shields, S.Lang, BethanVincent, Angela V.2020-10-15T22:22:42Z2020-10-15T22:22:42Z20201365-2990http://hdl.handle.net/20.500.12495/4463https://doi.org/10.1111/nan.12666instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coapplication/pdfengWiley-BlackwellNeuropathology and applied neurobiologyNeuropathology and applied neurobiology, 1365-2990, 2020https://onlinelibrary.wiley.com/doi/full/10.1111/nan.12666Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Acceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2020-09-10Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in miceSystemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in miceArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85Animal modelAntibody-mediated autoimmune diseaseGlycine receptorPERMProgressive encephalomyelitis with rigidity and myoclonusStiff person syndromeAims 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.ORIGINALA. Carvajal‐González L. Jacobson_2020.pdfA. Carvajal‐González L. Jacobson_2020.pdfapplication/pdf870261https://repositorio.unbosque.edu.co/bitstreams/891c075e-3ba2-40b0-a03e-955ae693270e/downloade69d740b3b7573e38c1af886d26839e8MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8908https://repositorio.unbosque.edu.co/bitstreams/cdb265ef-7680-4784-86ad-21490f973524/download0175ea4a2d4caec4bbcc37e300941108MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/1e9d3ceb-b29b-45b5-86c7-624b57cfa734/download8a4605be74aa9ea9d79846c1fba20a33MD53THUMBNAILA. Carvajal‐González L. Jacobson_2020.pdf.jpgA. Carvajal‐González L. Jacobson_2020.pdf.jpgIM Thumbnailimage/jpeg10056https://repositorio.unbosque.edu.co/bitstreams/2beb5a67-122c-4498-96f4-25983b32ce6f/download971185d9877e006b1e868cacc433e188MD54TEXTA. Carvajal‐González L. Jacobson_2020.pdf.txtA. Carvajal‐González L. 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