NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson's disease
NRSF is an essential mediator for the neuroprotection of trichostatin A in the MPTP mouse model of Parkinson's disease
复制标题
NRSF 是帕金森病 MPTP 小鼠模型中曲古抑菌素 A 神经保护的重要介质
DOI：
10.1016/j.neuropharm.2015.07.015
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发表时间：
2015-12-01
影响因子：
4.7
通讯作者：
Huang, Fang
中科院分区：
文献类型：
--
作者：
Suo, Haiyun;Wang, Pan;Huang, Fang
神经元限制性沉默因子（NRSF）可阻断非神经元细胞和神经干细胞中许多神经元基因的表达。越来越多的证据表明NRSF在成熟神经元中发挥作用，并在各种神经系统疾病中发挥关键作用。我们的前期研究表明，1-甲基-4-苯基吡啶离子（MPP+）处理的SH-SY 5 Y细胞中，NRSF靶基因脑源性神经营养因子（BDNF）和酪氨酸羟化酶（TH）的表达短暂降低。NRSF神经元缺陷小鼠对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）更敏感。在这里，我们研究了帕金森病（PD）体外和体内模型中表观遗传调节对NRSF靶基因表达的影响。进一步用曲古抑菌素A（TSA）研究组蛋白去乙酰化酶抑制剂对NRSF介导的阻遏作用的影响。我们发现TSA在体外可以解除NRSF靶基因的阻遏。单剂量TSA预处理还上调TH和BDNF的表达，并保护黑质纹状体多巴胺能通路免受MPTP诱导的野生型小鼠变性。然而，TSA的保护功能在NRSF神经元缺陷小鼠中被完全消除。我们的研究结果表明，NRSF作为一个必不可少的介质TSA的神经保护MPTP模型的PD。(C)2015爱思唯尔有限公司版权所有。
Neuron-restrictive silencer factor (NRSF) blocks the expression of many neuronal genes in non-neuronal cells and neural stem cells. There is growing body of evidence that NRSF functions in mature neurons and plays critical roles in various neurological disorders. Our previous study demonstrated that the expression of NRSF target genes brain-derived neurotrophic factor (BDNF), and tyrosine hydroxylase (TH) is transiently decreased in 1-methyl-4-phenyl-pyridinium ion (MPP+)-treated SH-SY5Y cells. NRSF neuronal deficient mice are more vulnerable to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here we investigated the effect of epigenetic modulation on the expression of NRSF target genes in in vitro and in vivo models of Parkinson's disease (PD). Trichostatin A (TSA) was further used to study the effects of histone deacetylase inhibition on NRSF-mediated repression. We found that the repression of NRSF target genes was relieved by TSA in vitro. A single dose TSA pretreatment also upregulated the expression of TH and BDNF and protected the nigrostriatal dopaminergic pathway against MPTP-induced degeneration in wild type mice. However, the protective functions of TSA were fully abolished in NRSF neuronal deficient mice. Our results suggest that NRSF serves as an essential mediator for the neuro-protection of TSA in the MPTP model of PD. (C) 2015 Elsevier Ltd. All rights reserved.