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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration
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Platelet-activating factor receptor knockout mice are protected from MPTP-induced dopaminergic degeneration

机译：血小板活化因子受体基因敲除小鼠免受MPTP诱导的多巴胺能变性

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摘要

Platelet-activating factor (PAF), a potent mediator of inflammatory and immune responses, plays various roles in neuronal functions. However, little is known about the role of PAF/platelet-activating factor receptor (PAF-R) in Parkinson's disease. Treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) resulted in significant increases in PAF species in the striatum of wild-type mice. These increases paralleled PAF-R gene expression in wild-type mice. Although nuclear factor kappa B (NF-κB) DNA-binding activity was increased significantly in MPTP-treated wild-type mice, this increase was not significant in PAF-R antagonist ginkgolide B (GB)-treated mice or PAF-R knockout (PAF-R-/-) mice. Pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, significantly ameliorated the dopaminergic deficits induced by MPTP in wild-type mice. MPTP treatment significantly increased oxidative damage, the immunoreactivity of ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglial cells, and microglial differentiation of the M1 type in the striatum of wild-type mice. Consistently, PDTC significantly attenuated MPTP-induced behavioral impairments in wild-type mice. However, dopaminergic deficits, oxidative damage, reactive microglial cells, and behavioral impairments induced by MPTP were not significantly observed in GB-treated mice or PAF-R -/- mice. PDTC did not significantly alter the attenuations evident in MPTP-treated PAF-R-/- mice, indicating that NF-κB is a critical target for neurotoxic modulation of PAF-R. We propose for the first time that PAF/PAF-R can mediate dopaminergic degeneration via an NF-κB-dependent signaling process.
机译：血小板激活因子（PAF）是炎症和免疫反应的有效介体，在神经元功能中起多种作用。然而，关于PAF /血小板活化因子受体（PAF-R）在帕金森氏病中的作用知之甚少。用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理导致野生型小鼠纹状体中PAF种类显着增加。这些在野生型小鼠中平行的PAF-R基因表达增加。尽管在MPTP处理的野生型小鼠中核因子κB（NF-κB）DNA结合活性显着增加，但在PAF-R拮抗剂银杏内酯B（GB）处理的小鼠或PAF-R敲除小鼠中这种增加并不明显（ PAF-R-/-）小鼠。吡咯烷二硫代氨基甲酸酯（PDTC）是一种NF-κB抑制剂，可显着改善MPTP在野生型小鼠中引起的多巴胺能缺陷。 MPTP处理可显着增加氧化损伤，离子化钙结合衔接子分子1（Iba-1）阳性的小胶质细胞的免疫反应性，以及野生型小鼠纹状体中M1型的小胶质细胞分化。一致地，PDTC显着减轻了野生型小鼠中MPTP诱导的行为障碍。但是，在GB治疗的小鼠或PAF-R-/-小鼠中，没有明显观察到MPTP诱导的多巴胺能缺陷，氧化损伤，小胶质细胞反应性和行为障碍。 PDTC并未显着改变MPTP处理的PAF-R-/-小鼠中明显的衰减，表明NF-κB是PAF-R神经毒性调节的关键靶标。我们首次提出PAF / PAF-R可通过依赖NF-κB的信号传导过程介导多巴胺能变性。

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