• Media type: E-Article
  • Title: Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice
  • Contributor: Kunze, Lea Helena; Ruch, François; Biechele, Gloria; Eckenweber, Florian; Wind-Mark, Karin; Dinkel, Lina; Feyen, Paul; Bartenstein, Peter; Ziegler, Sibylle; Paeger, Lars; Tahirovic, Sabina; Herms, Jochen; Brendel, Matthias
  • Published: MDPI AG, 2023
  • Published in: International Journal of Molecular Sciences, 24 (2023) 12, Seite 10106
  • Language: English
  • DOI: 10.3390/ijms241210106
  • ISSN: 1422-0067
  • Origination:
  • Footnote:
  • Description: 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 recent years, the peroxisome proliferator-activated receptor γ (PPARγ) has 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.
  • Access State: Open Access