Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice
| Autor: | Lea Helena Kunze, François Ruch, Gloria Biechele, Florian Eckenweber, Karin Wind-Mark, Lina Dinkel, Paul Feyen, Peter Bartenstein, Sibylle Ziegler, Lars Paeger, Sabina Tahirovic, Jochen Herms, Matthias Brendel |
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| Rok vydání: | 2023 |
| Předmět: |
Amyloid beta-Peptides
Pioglitazone pharmacology [Pioglitazone] metabolism [Amyloid beta-Peptides] microglia Mice Transgenic tau Proteins metabolism [Microglia] metabolism [tau Proteins] PPAR gamma Mice Disease Models Animal TSPO-PET ddc:540 Animals metabolism [Tauopathies] metabolism [PPAR gamma] metabolism [Alzheimer Disease] |
| Zdroj: | International journal of molecular sciences 24(12), 10106 (2023). doi:10.3390/ijms241210106 special issue: "Neuroinflammation in the Pathogenesis of Alzheimer's Disease and Related Dementias" |
| DOI: | 10.20944/preprints202304.1153.v1 |
| Popis: | Neuroinflammation is one disease hallmark on the road to neurodegeneration in primary tauopathies. Thus, immunomodulation might be a suitable treatment strategy to delay or even prevent the occurrence of symptoms and thus relieve the burden for patients and caregivers. In the last years, the peroxisome proliferator-activated receptor γ (PPARγ) received increasing attention as it is immediately involved in the regulation of the immune system and can be targeted by the anti-diabetic drug pioglitazone. Previous studies have shown significant immunomodulation in amyloid-β (Aβ) mouse models by pioglitazone. In this study, we performed long-term treatment over six months in P301S mice as a tauopathy model with either pioglitazone or placebo. We performed serial 18 kDa translocator protein positron-emission-tomography (TSPO-PET) imaging and terminal immunohistochemistry to assess microglial activation during treatment. Tau pathology was quantified via immunohistochemistry at the end of the study. Long-term pioglitazone treatment had no significant effect on TSPO-PET, immunohistochemistry read-outs of microglial activation, or tau pathology levels in P301S mice. Thus, we conclude that pioglitazone modifies the time course of Aβ-dependent microglial activation, but does not significantly modulate microglial activation in response to tau pathology. |
| Databáze: | OpenAIRE |
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