Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae

Rukshan A Rafeek; Catherine M Lobbe; Ethan C Wilkinson; Adam S Hamlin; Nicholas M Andronicos; David McMillan; Kadaba Srinivasa Sriprakash; Natkunam Ketheesan

doi:10.1002/ame2.12164

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Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae

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Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae

Rukshan A Rafeek, Catherine M Lobbe, Ethan C Wilkinson, Adam S Hamlin, Nicholas M Andronicos, David McMillan, Kadaba Srinivasa Sriprakash and Natkunam Ketheesan

Animal Models and Experimental Medicine, Vol.4(2), pp.151-161

2021

DOI: https://doi.org/10.1002/ame2.12164

PMCID: PMC8212825

PMID: 34179722

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Abstract

animal model

group A streptococcus

Lewis rats

rheumatic fever

rheumatic heart disease

sydenham chorea (SC)

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.

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Title: Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae
Authors: Rukshan A Rafeek (Author) - University of New England
Catherine M Lobbe (Author) - University of New England
Ethan C Wilkinson (Author) - University of New England
Adam S Hamlin (Author) - University of New England
Nicholas M Andronicos (Author) - University of New England
David McMillan (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Kadaba Srinivasa Sriprakash (Author) - University of New England
Natkunam Ketheesan (Corresponding Author) - University of New England
Publication details: Animal Models and Experimental Medicine, Vol.4(2), pp.151-161
Publisher: John Wiley & Sons, Inc.
Date published: 2021
DOI: 10.1002/ame2.12164
ISSN: 2576-2095
PMID: 34179722; PMC8212825
Copyright note: © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 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.
Organisation Unit: University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99523408402621
Output Type: Journal article

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