Alterations of gene expression of sodium channels in dorsal root ganglion neurons of estrogen receptor knockout (ERKO) mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
Alterations of gene expression of sodium channels in dorsal root ganglion neurons of estrogen receptor knockout (ERKO) mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
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DOI：
10.1007/s12020-012-9637-8
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发表时间：
2012-08-01
期刊：
影响因子：
3.7
通讯作者：
Xiao, Hang
中科院分区：
文献类型：
--
作者：
Ding, Haixia;Wang, Qiang;Xiao, Hang
雌激素受体（ER α和ER β）介导雌激素对MPTP诱导的纹状体多巴胺（DA）耗竭的神经保护作用。疼痛是帕金森病（PD）的一个重要和痛苦的症状。感觉神经元中的电压门控钠通道参与神经病理性疼痛的发展。本研究探讨MPTP对ER基因敲除（ERKO）小鼠背根神经节（DRG）神经元伤害性感受和电压门控钠通道基因表达的影响。我们发现对WT小鼠施用MPTP（11 mg/kg）导致DA及其两种代谢物的广泛消耗，观察到α ERKO小鼠比β ERKO或WT小鼠更容易受到MPTP毒性的影响。此外，我们发现TTX-S和TTX-R钠通道亚型的mRNA水平在MPTP处理的WT动物中受到不同的影响。MPTP诱导的DRG神经元Nav1.1和Nav1.9的上调，Nav1.6的下调可能是通过ER β实现的，Nav1.7的上调和Nav1.8的下调可能同时依赖于ER α和ER β。因此，MPTP诱导的DRG神经元钠通道基因表达的改变可能是影响兴奋性和伤害性阈值的重要机制，ER在PD的伤害性感受中起作用。
Estrogen receptors (ER alpha and ER beta) mediate the neuroprotection of estrogens against MPTP-induced striatal dopamine (DA) depletion. Pain is an important and distressing symptom in Parkinson's disease (PD). Voltage-gated sodium channels in sensory neurons are involved in the development of neuropathic pain. In this study, MPTP caused changes in nociception and alterations of gene expression of voltage-gated sodium channels in dorsal root ganglion (DRG) neurons in ER knockout (ERKO) mice were investigated. We found that administration of MPTP (11 mg/kg) to WT mice led to an extensive depletion of DA and its two metabolites, alpha ERKO mice were observed to be more susceptible to MPTP toxicity than beta ERKO or WT mice. In addition, we found that the mRNA levels of TTX-S and TTX-R sodium channel subtypes were differentially affected in MPTP-treated WT animals. The MPTP-induced up-regulation of Nav1.1 and Nav1.9, down-regulation of Nav1.6 in DRG neurons may be through ER beta, up-regulation of Nav1.7 and down-regulation of Nav1.8 are dependent on both ER alpha and ER beta. Therefore, the MPTP-induced alterations of gene expression of sodium channels in DRG neurons could be an important mechanism to affect excitability and nociceptive thresholds, and the ERs appear to play a role in nociception in PD.