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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 principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873718/ https://www.ncbi.nlm.nih.gov/pubmed/32910464 http://dx.doi.org/10.1111/nan.12666 |
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author | Carvajal‐González, A. Jacobson, L. Clover, L. Wickremaratchi, M. Shields, S. Lang, B. Vincent, A. |
author_facet | Carvajal‐González, A. Jacobson, L. Clover, L. Wickremaratchi, M. Shields, S. Lang, B. Vincent, A. |
author_sort | Carvajal‐González, A. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7873718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78737182021-02-17 Systemic delivery of human GlyR IgG antibody induces GlyR internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice Carvajal‐González, A. Jacobson, L. Clover, L. Wickremaratchi, M. Shields, S. Lang, B. Vincent, A. Neuropathol Appl Neurobiol Original Articles 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. John Wiley and Sons Inc. 2020-09-28 2021-02 /pmc/articles/PMC7873718/ /pubmed/32910464 http://dx.doi.org/10.1111/nan.12666 Text en © 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Carvajal‐González, A. Jacobson, L. Clover, L. Wickremaratchi, M. Shields, S. Lang, B. Vincent, A. 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 |
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_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_sort | systemic delivery of human glyr igg antibody induces glyr internalization into motor neurons of brainstem and spinal cord with motor dysfunction in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873718/ https://www.ncbi.nlm.nih.gov/pubmed/32910464 http://dx.doi.org/10.1111/nan.12666 |
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