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Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition

We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would re...

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Autores principales: Blume, Tanja, Deussing, Maximilian, Biechele, Gloria, Peters, Finn, Zott, Benedikt, Schmidt, Claudio, Franzmeier, Nicolai, Wind, Karin, Eckenweber, Florian, Sacher, Christian, Shi, Yuan, Ochs, Katharina, Kleinberger, Gernot, Xiang, Xianyuan, Focke, Carola, Lindner, Simon, Gildehaus, Franz-Josef, Beyer, Leonie, von Ungern-Sternberg, Barbara, Bartenstein, Peter, Baumann, Karlheinz, Adelsberger, Helmuth, Rominger, Axel, Cumming, Paul, Willem, Michael, Dorostkar, Mario M., Herms, Jochen, Brendel, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007038/
https://www.ncbi.nlm.nih.gov/pubmed/35431893
http://dx.doi.org/10.3389/fnagi.2022.854031
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author Blume, Tanja
Deussing, Maximilian
Biechele, Gloria
Peters, Finn
Zott, Benedikt
Schmidt, Claudio
Franzmeier, Nicolai
Wind, Karin
Eckenweber, Florian
Sacher, Christian
Shi, Yuan
Ochs, Katharina
Kleinberger, Gernot
Xiang, Xianyuan
Focke, Carola
Lindner, Simon
Gildehaus, Franz-Josef
Beyer, Leonie
von Ungern-Sternberg, Barbara
Bartenstein, Peter
Baumann, Karlheinz
Adelsberger, Helmuth
Rominger, Axel
Cumming, Paul
Willem, Michael
Dorostkar, Mario M.
Herms, Jochen
Brendel, Matthias
author_facet Blume, Tanja
Deussing, Maximilian
Biechele, Gloria
Peters, Finn
Zott, Benedikt
Schmidt, Claudio
Franzmeier, Nicolai
Wind, Karin
Eckenweber, Florian
Sacher, Christian
Shi, Yuan
Ochs, Katharina
Kleinberger, Gernot
Xiang, Xianyuan
Focke, Carola
Lindner, Simon
Gildehaus, Franz-Josef
Beyer, Leonie
von Ungern-Sternberg, Barbara
Bartenstein, Peter
Baumann, Karlheinz
Adelsberger, Helmuth
Rominger, Axel
Cumming, Paul
Willem, Michael
Dorostkar, Mario M.
Herms, Jochen
Brendel, Matthias
author_sort Blume, Tanja
collection PubMed
description We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would rescue from increases of the Aβ-PET signal while promoting spatial learning and preservation of synaptic density. Here, we investigated longitudinally for 5 months PS2APP mice (N = 23; baseline age: 8 months) and App(NL–G–F) mice (N = 37; baseline age: 5 months) using Aβ-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. Surprisingly, Aβ-PET and immunohistochemistry revealed a shift toward higher fibrillary composition of Aβ-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. These translational data suggest that a shift toward higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the Aβ-PET signal upon immunomodulatory treatments targeting Aβ aggregation can thus be protective.
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spelling pubmed-90070382022-04-14 Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition Blume, Tanja Deussing, Maximilian Biechele, Gloria Peters, Finn Zott, Benedikt Schmidt, Claudio Franzmeier, Nicolai Wind, Karin Eckenweber, Florian Sacher, Christian Shi, Yuan Ochs, Katharina Kleinberger, Gernot Xiang, Xianyuan Focke, Carola Lindner, Simon Gildehaus, Franz-Josef Beyer, Leonie von Ungern-Sternberg, Barbara Bartenstein, Peter Baumann, Karlheinz Adelsberger, Helmuth Rominger, Axel Cumming, Paul Willem, Michael Dorostkar, Mario M. Herms, Jochen Brendel, Matthias Front Aging Neurosci Aging Neuroscience We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would rescue from increases of the Aβ-PET signal while promoting spatial learning and preservation of synaptic density. Here, we investigated longitudinally for 5 months PS2APP mice (N = 23; baseline age: 8 months) and App(NL–G–F) mice (N = 37; baseline age: 5 months) using Aβ-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. Surprisingly, Aβ-PET and immunohistochemistry revealed a shift toward higher fibrillary composition of Aβ-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. These translational data suggest that a shift toward higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the Aβ-PET signal upon immunomodulatory treatments targeting Aβ aggregation can thus be protective. Frontiers Media S.A. 2022-03-30 /pmc/articles/PMC9007038/ /pubmed/35431893 http://dx.doi.org/10.3389/fnagi.2022.854031 Text en Copyright © 2022 Blume, Deussing, Biechele, Peters, Zott, Schmidt, Franzmeier, Wind, Eckenweber, Sacher, Shi, Ochs, Kleinberger, Xiang, Focke, Lindner, Gildehaus, Beyer, von Ungern-Sternberg, Bartenstein, Baumann, Adelsberger, Rominger, Cumming, Willem, Dorostkar, Herms and Brendel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Blume, Tanja
Deussing, Maximilian
Biechele, Gloria
Peters, Finn
Zott, Benedikt
Schmidt, Claudio
Franzmeier, Nicolai
Wind, Karin
Eckenweber, Florian
Sacher, Christian
Shi, Yuan
Ochs, Katharina
Kleinberger, Gernot
Xiang, Xianyuan
Focke, Carola
Lindner, Simon
Gildehaus, Franz-Josef
Beyer, Leonie
von Ungern-Sternberg, Barbara
Bartenstein, Peter
Baumann, Karlheinz
Adelsberger, Helmuth
Rominger, Axel
Cumming, Paul
Willem, Michael
Dorostkar, Mario M.
Herms, Jochen
Brendel, Matthias
Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title_full Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title_fullStr Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title_full_unstemmed Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title_short Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
title_sort chronic pparγ stimulation shifts amyloidosis to higher fibrillarity but improves cognition
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007038/
https://www.ncbi.nlm.nih.gov/pubmed/35431893
http://dx.doi.org/10.3389/fnagi.2022.854031
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