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Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats

Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage...

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Autores principales: Ceyzériat, Kelly, Zilli, Thomas, Millet, Philippe, Koutsouvelis, Nikolaos, Dipasquale, Giovanna, Fossey, Christine, Cailly, Thomas, Fabis, Frédéric, Frisoni, Giovanni B., Garibotto, Valentina, Tournier, Benjamin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783748/
https://www.ncbi.nlm.nih.gov/pubmed/36550510
http://dx.doi.org/10.1186/s12974-022-02673-x
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author Ceyzériat, Kelly
Zilli, Thomas
Millet, Philippe
Koutsouvelis, Nikolaos
Dipasquale, Giovanna
Fossey, Christine
Cailly, Thomas
Fabis, Frédéric
Frisoni, Giovanni B.
Garibotto, Valentina
Tournier, Benjamin B.
author_facet Ceyzériat, Kelly
Zilli, Thomas
Millet, Philippe
Koutsouvelis, Nikolaos
Dipasquale, Giovanna
Fossey, Christine
Cailly, Thomas
Fabis, Frédéric
Frisoni, Giovanni B.
Garibotto, Valentina
Tournier, Benjamin B.
author_sort Ceyzériat, Kelly
collection PubMed
description Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01; soluble and aggregated forms of Aβ(40), Aβ(42), and Aβ(oligomers)). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02673-x.
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spelling pubmed-97837482022-12-24 Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats Ceyzériat, Kelly Zilli, Thomas Millet, Philippe Koutsouvelis, Nikolaos Dipasquale, Giovanna Fossey, Christine Cailly, Thomas Fabis, Frédéric Frisoni, Giovanni B. Garibotto, Valentina Tournier, Benjamin B. J Neuroinflammation Research Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01; soluble and aggregated forms of Aβ(40), Aβ(42), and Aβ(oligomers)). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02673-x. BioMed Central 2022-12-22 /pmc/articles/PMC9783748/ /pubmed/36550510 http://dx.doi.org/10.1186/s12974-022-02673-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ceyzériat, Kelly
Zilli, Thomas
Millet, Philippe
Koutsouvelis, Nikolaos
Dipasquale, Giovanna
Fossey, Christine
Cailly, Thomas
Fabis, Frédéric
Frisoni, Giovanni B.
Garibotto, Valentina
Tournier, Benjamin B.
Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title_full Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title_fullStr Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title_full_unstemmed Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title_short Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
title_sort low-dose brain irradiation normalizes tspo and clusterin levels and promotes the non-amyloidogenic pathway in pre-symptomatic tgf344-ad rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783748/
https://www.ncbi.nlm.nih.gov/pubmed/36550510
http://dx.doi.org/10.1186/s12974-022-02673-x
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