Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson's and Alzheimer's disease
Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson's and Alzheimer's disease
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DOI：
10.1007/s00441-017-2626-8
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发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Galter, Dagmar
中科院分区：
文献类型：
--
作者：
Gellhaar, Sandra;Sunnemark, Dan;Galter, Dagmar
髓过氧化物酶（MPO）是炎症和退行性过程中的关键酶，尽管关于其在脑中的表达的报道相互矛盾。我们研究了MPO的细胞定位，并比较了神经系统健康个体与帕金森病（PD）或阿尔茨海默病（AD; n = 10-25）患者不同脑区MPO细胞的数量。我们还研究了两种啮齿动物PD模型。MPO免疫反应（ir）在单核细胞，血管周围的巨噬细胞和变形小胶质细胞在人脑实质中检测到，而没有观察到与胶质细胞酸性蛋白（GFAP）的IR共定位。在中脑，尾状核和壳核，我们发现一个显着增加的MPO免疫反应细胞在PD与对照组相比，而在小脑，没有明显的差异。在PD或对照组中，神经元和偶尔的小β-淀粉样蛋白免疫反应性斑块中均未检测到MPO免疫反应。在AD患者的额叶皮层中，我们发现与对照组相比，有更多的MPO免疫反应阳性细胞，细胞外斑块中有强烈的MPO免疫反应。在部分AD患者的海马中，部分锥体神经元可见MPO样免疫反应。无论是在大鼠PD模型中的快速多巴胺耗竭，还是在MitoPark小鼠中的多巴胺神经元的缓慢变性，都不会诱导任何脑区域中MPO ir的表达。在任何人类或啮齿类动物脑区，尽管骨髓髓样细胞显示出清晰的MPO信号，但用放射性原位杂交检测不到MPO mRNA。我们的研究结果表明，在PD和AD中受神经变性影响的脑区MPO免疫反应细胞显著增加，支持MPO抑制剂在新治疗策略中的研究。
Myeloperoxidase (MPO) is a key enzyme in inflammatory and degenerative processes, although conflicting reports have been presented concerning its expression in the brain. We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically healthy individuals and patients with Parkinson's disease (PD) or Alzheimer's disease (AD; n = 10-25). We also investigated two rodent PD models. MPO immunoreactivity (ir) was detected in monocytes, perivascular macrophages and amoeboid microglia in the human brain parenchyma, whereas no co-localization with glial fibrillary acidic protein (GFAP) ir was observed. In the midbrain, caudate and putamen, we found a significant increase of MPO-immunoreactive cells in PD compared with control brains, whereas in the cerebellum, no difference was apparent. MPO ir was detected neither in neurons nor in occasional small beta-amyloid-immunoreactive plaques in PD or control cases. In the frontal cortex of AD patients, we found significantly more MPO-immunoreactive cells compared with control cases, together with intense MPO ir in extracellular plaques. In the hippocampus of several AD cases, MPO-like ir was observed in some pyramidal neurons. Neither rapid dopamine depletion in the rat PD model, nor slow degeneration of dopamine neurons in MitoPark mice induced the expression of MPO ir in any brain region. MPO mRNA was not detectable with radioactive in situ hybridization in any human or rodent brain area, although myeloid cells from bone marrow displayed clear MPO signals. Our results indicate significant increases of MPO-immunoreactive cells in brain regions affected by neurodegeneration in PD and AD, supporting investigations of MPO inhibitors in novel treatment strategies.