Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
| Autor: | Paul Cumming, Axel Rominger, Maximilian Deussing, Xianyuan Xiang, Claudio Schmidt, Leonie Beyer, Gernot Kleinberger, Helmuth Adelsberger, Karin Wind, Katharina Ochs, Christian Sacher, Nicolai Franzmeier, Yuan Shi, Carola Focke, Franz-Josef Gildehaus, Benedikt Zott, Simon Lindner, Finn Peters, Michael Willem, von Ungern-Sternberg B, Tanja Blume, Peter Bartenstein, Matthias Brendel, Mario M. Dorostkar, Karlheinz Baumann, Florian Eckenweber, Gloria Biechele, Jochen Herms |
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| Rok vydání: | 2021 |
| Předmět: |
Genetically modified mouse
Agonist medicine.medical_specialty medicine.diagnostic_test business.industry medicine.drug_class Amyloidosis Stimulation medicine.disease Endocrinology Positron emission tomography Internal medicine medicine Immunohistochemistry business Receptor Pioglitazone medicine.drug |
| DOI: | 10.1101/2021.05.30.446348 |
| Popis: | BackgroundWe 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.MethodsPS2APP mice (N=23; baseline age: 8 months) and AppNL-G-F mice (N=37; baseline age: 5 months) were investigated longitudinally for five 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.ResultsSurprisingly, Aβ-PET and immunohistochemistry revealed a shift towards 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.ConclusionThese translational data suggest that a shift towards 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. |
| Databáze: | OpenAIRE |
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