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The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea

The increased awareness of obstructive sleep apnoea’s (OSA) links to Alzheimer’s disease and major psychiatric disorders has recently directed an intensified search for their potential shared mechanisms. We hypothesised that neuroinflammation and the microglial TLR2-system may act as a core process...

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Autores principales: Polsek, Dora, Cash, Diana, Veronese, Mattia, Ilic, Katarina, Wood, Tobias C., Milosevic, Milan, Kalanj-Bognar, Svjetlana, Morrell, Mary J., Williams, Steve C. R., Gajovic, Srecko, Leschziner, Guy D., Mitrecic, Dinko, Rosenzweig, Ivana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351955/
https://www.ncbi.nlm.nih.gov/pubmed/32651433
http://dx.doi.org/10.1038/s41598-020-68299-2
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author Polsek, Dora
Cash, Diana
Veronese, Mattia
Ilic, Katarina
Wood, Tobias C.
Milosevic, Milan
Kalanj-Bognar, Svjetlana
Morrell, Mary J.
Williams, Steve C. R.
Gajovic, Srecko
Leschziner, Guy D.
Mitrecic, Dinko
Rosenzweig, Ivana
author_facet Polsek, Dora
Cash, Diana
Veronese, Mattia
Ilic, Katarina
Wood, Tobias C.
Milosevic, Milan
Kalanj-Bognar, Svjetlana
Morrell, Mary J.
Williams, Steve C. R.
Gajovic, Srecko
Leschziner, Guy D.
Mitrecic, Dinko
Rosenzweig, Ivana
author_sort Polsek, Dora
collection PubMed
description The increased awareness of obstructive sleep apnoea’s (OSA) links to Alzheimer’s disease and major psychiatric disorders has recently directed an intensified search for their potential shared mechanisms. We hypothesised that neuroinflammation and the microglial TLR2-system may act as a core process at the intersection of their pathophysiology. Moreover, we postulated that inflammatory-response might underlie development of key behavioural and neurostructural changes in OSA. Henceforth, we set out to investigate effects of 3 weeks’ exposure to chronic intermittent hypoxia in mice with or without functional TRL2 (TLR2(+/+), C57BL/6-Tyrc-Brd-Tg(Tlr2-luc/gfp)Kri/Gaj;TLR2(−/−),C57BL/6-Tlr2tm1Kir). By utilising multimodal imaging in this established model of OSA, a discernible neuroinflammatory response was demonstrated for the first time. The septal nuclei and forebrain were shown as the initial key seed-sites of the inflammatory cascade that led to wider structural changes in the associated neurocircuitry. Finally, the modulatory role for the functional TLR2-system was suggested in aetiology of depressive, anxious and anorexiolytic symptoms in OSA.
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spelling pubmed-73519552020-07-14 The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea Polsek, Dora Cash, Diana Veronese, Mattia Ilic, Katarina Wood, Tobias C. Milosevic, Milan Kalanj-Bognar, Svjetlana Morrell, Mary J. Williams, Steve C. R. Gajovic, Srecko Leschziner, Guy D. Mitrecic, Dinko Rosenzweig, Ivana Sci Rep Article The increased awareness of obstructive sleep apnoea’s (OSA) links to Alzheimer’s disease and major psychiatric disorders has recently directed an intensified search for their potential shared mechanisms. We hypothesised that neuroinflammation and the microglial TLR2-system may act as a core process at the intersection of their pathophysiology. Moreover, we postulated that inflammatory-response might underlie development of key behavioural and neurostructural changes in OSA. Henceforth, we set out to investigate effects of 3 weeks’ exposure to chronic intermittent hypoxia in mice with or without functional TRL2 (TLR2(+/+), C57BL/6-Tyrc-Brd-Tg(Tlr2-luc/gfp)Kri/Gaj;TLR2(−/−),C57BL/6-Tlr2tm1Kir). By utilising multimodal imaging in this established model of OSA, a discernible neuroinflammatory response was demonstrated for the first time. The septal nuclei and forebrain were shown as the initial key seed-sites of the inflammatory cascade that led to wider structural changes in the associated neurocircuitry. Finally, the modulatory role for the functional TLR2-system was suggested in aetiology of depressive, anxious and anorexiolytic symptoms in OSA. Nature Publishing Group UK 2020-07-10 /pmc/articles/PMC7351955/ /pubmed/32651433 http://dx.doi.org/10.1038/s41598-020-68299-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Polsek, Dora
Cash, Diana
Veronese, Mattia
Ilic, Katarina
Wood, Tobias C.
Milosevic, Milan
Kalanj-Bognar, Svjetlana
Morrell, Mary J.
Williams, Steve C. R.
Gajovic, Srecko
Leschziner, Guy D.
Mitrecic, Dinko
Rosenzweig, Ivana
The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title_full The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title_fullStr The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title_full_unstemmed The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title_short The innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
title_sort innate immune toll-like-receptor-2 modulates the depressogenic and anorexiolytic neuroinflammatory response in obstructive sleep apnoea
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351955/
https://www.ncbi.nlm.nih.gov/pubmed/32651433
http://dx.doi.org/10.1038/s41598-020-68299-2
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