Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice

Lea Helena Kunze
ORCID logo ,
François Ruch
,
Gloria Biechele
ORCID logo ,
Florian Eckenweber
,
Karin Wind-Mark
,
Lina Dinkel
,
Paul Feyen
,
Peter Bartenstein
,
Sibylle Ziegler
,
Lars Paeger
,
Sabina Tahirovic
ORCID logo ,
Jochen Herms
,
Matthias Brendel
*
Version 1 : Received: 28 April 2023 / Approved: 28 April 2023 / Online: 28 April 2023 (08:56:28 CEST)

A peer-reviewed article of this Preprint also exists.

Kunze, L.H.; Ruch, F.; Biechele, G.; Eckenweber, F.; Wind-Mark, K.; Dinkel, L.; Feyen, P.; Bartenstein, P.; Ziegler, S.; Paeger, L.; Tahirovic, S.; Herms, J.; Brendel, M. Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice. Int. J. Mol. Sci. 2023, 24, 10106. Kunze, L.H.; Ruch, F.; Biechele, G.; Eckenweber, F.; Wind-Mark, K.; Dinkel, L.; Feyen, P.; Bartenstein, P.; Ziegler, S.; Paeger, L.; Tahirovic, S.; Herms, J.; Brendel, M. Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice. Int. J. Mol. Sci. 2023, 24, 10106.

Abstract

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.

Keywords

microglia; pioglitazone; TSPO-PET

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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