PPAR-γ agonist pioglitazone reduces microglial proliferation and NF-κB activation in the substantia nigra in the 6-hydroxydopamine model of Parkinson's disease
PPAR-γ agonist pioglitazone reduces microglial proliferation and NF-κB activation in the substantia nigra in the 6-hydroxydopamine model of Parkinson's disease
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DOI：
10.1016/j.pharep.2018.11.005
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发表时间：
2019-08-01
影响因子：
4.4
通讯作者：
Barbato Frazao Vital, Maria Aparecida
中科院分区：
文献类型：
--
作者：
Forcelini Machado, Meira Maria;Bassani, Taysa Bervian;Barbato Frazao Vital, Maria Aparecida
背景资料：过氧化物酶体增殖物激活受体γ（PPAR-gamma）激动剂由于其减少细胞死亡和阻止神经变性进展的神经保护和抗炎作用而在研究中受到广泛关注。因此，本研究观察了吡格列酮对6-羟基多巴胺（6-OHDA）laser.Methods后的主要炎症标志物的影响：5天的PPAR-gamma激动剂吡格列酮（30 mg/kg）在雄性Wistar大鼠接受双侧intrinigral输注6-OHDA的影响。术后第1、7、14、21天进行旷场实验。在第21天的行为测试后，立即将大鼠安乐死，并去除黑质以通过western blot分析核因子κ B（NF-κ B）和I κ B的表达。免疫组化，动物心内灌注，与脑切除，被冷冻和切片，被选择的切片的SNc区域检测酪氨酸羟化酶（TH）免疫反应性，小胶质细胞活化（Iba-1）和NF-κ B B易位在nucleus.Results：吡格列酮保护大鼠hypolocomotion和6-OHDA诱导的多巴胺能神经变性的第7天。观察到小胶质细胞活化和NF-κ B表达的减少，p65活化被抑制。结论：这些结果表明，吡格列酮可能是一个潜在的辅助治疗帕金森氏病，因为它对神经变性进展的病理标志物的影响。(C)2018年波兰科学院药理学主要研究所。Elsevier B. V.出版，保留所有权利。
Background: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) 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-gamma 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 kappa B (NF-kappa B) and I kappa B 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-kappa B 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-kappa B 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. (C) 2018 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.