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Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae
BACKGROUND: The neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212825/ https://www.ncbi.nlm.nih.gov/pubmed/34179722 http://dx.doi.org/10.1002/ame2.12164 |
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author | Rafeek, Rukshan A. M. Lobbe, Catherine M. Wilkinson, Ethan C. Hamlin, Adam S. Andronicos, Nicholas M. McMillan, David J. Sriprakash, Kadaba S. Ketheesan, Natkunam |
author_facet | Rafeek, Rukshan A. M. Lobbe, Catherine M. Wilkinson, Ethan C. Hamlin, Adam S. Andronicos, Nicholas M. McMillan, David J. Sriprakash, Kadaba S. Ketheesan, Natkunam |
author_sort | Rafeek, Rukshan A. M. |
collection | PubMed |
description | BACKGROUND: The neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS). METHODS: Standard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive‐compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens. RESULTS: For control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age‐dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively. CONCLUSION: We have characterised a new model that provides longitudinal stability of age‐dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post‐streptococcal complications. |
format | Online Article Text |
id | pubmed-8212825 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82128252021-06-25 Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae Rafeek, Rukshan A. M. Lobbe, Catherine M. Wilkinson, Ethan C. Hamlin, Adam S. Andronicos, Nicholas M. McMillan, David J. Sriprakash, Kadaba S. Ketheesan, Natkunam Animal Model Exp Med Original Articles BACKGROUND: The neuropsychiatric disorders due to post‐streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS). METHODS: Standard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive‐compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens. RESULTS: For control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age‐dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively. CONCLUSION: We have characterised a new model that provides longitudinal stability of age‐dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post‐streptococcal complications. John Wiley and Sons Inc. 2021-04-08 /pmc/articles/PMC8212825/ /pubmed/34179722 http://dx.doi.org/10.1002/ame2.12164 Text en © 2021 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Rafeek, Rukshan A. M. Lobbe, Catherine M. Wilkinson, Ethan C. Hamlin, Adam S. Andronicos, Nicholas M. McMillan, David J. Sriprakash, Kadaba S. Ketheesan, Natkunam Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title | Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title_full | Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title_fullStr | Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title_full_unstemmed | Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title_short | Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
title_sort | group a streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post‐streptococcal autoimmune sequelae |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212825/ https://www.ncbi.nlm.nih.gov/pubmed/34179722 http://dx.doi.org/10.1002/ame2.12164 |
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