PPAR-γ agonist pioglitazone reduces microglial proliferation and NF-κB activation in the substantia nigra in the 6-hydroxydopamine model of Parkinson's disease

Abstract

Background: Peroxisome proliferator-activated receptor γ (PPAR-γ) agonists have received much attention in research because of their neuroprotective and anti-inflammatory effects that reduce cell death and halt the progression of neurodegeneration. Thus, this study observed the pioglitazone effects on the main inflammatory markers after 6-hydroxydopamine (6-OHDA) lesion.

Methods: The effects of a 5-day administration of the PPAR-γ agonist pioglitazone (30 mg/kg) in male Wistar rats that received bilateral intranigral infusions of 6-OHDA. After surgery, the rats were evaluated in the open-field test on days 1,7,14, and 21. Immediately after the behavioral tests on day 21, the rats were euthanized, and the substantia nigra was removed to analyze the expression of nuclear factor κB (NF-κB) and IκB by western blot. To immunohistochemical, animals were intracardially perfused, with brain removal that was frozen and sectioned, being selected slices of the SNc region to detect tyrosine hydroxylase (TH) immunoreactivity, microglia activation (Iba-1) and NF-κB translocation in the nucleus.

Results: Pioglitazone protected rats against hypolocomotion and 6-OHDA-induced dopaminergic neurodegeneration on day 7. Decreases in the microglial activation and the NF-κB expression were observed, and the p65 activation was inhibited.

Conclusions: These results suggest that pioglitazone may be a potential adjuvant for the treatment of Parkinson`s disease because of its effects on pathological markers of the progression of neurodegeneration.

Keywords: NF-κB; Neuroinflammation; PPAR-γ; Parkinson’s disease; Pioglitazone.