Preventive effects of AdR-siPTEN through the regulation of NMDA receptor NR2B subunit in trigeminal ganglia of migraine rats

Preventive effects of AdR-siPTEN through the regulation of NMDA receptor NR2B subunit in trigeminal ganglia of migraine rats
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AdR-siPTEN通过调节NMDA受体NR2B亚基对偏头痛大鼠三叉神经节的预防作用

DOI:
10.1179/1743132812y.0000000113
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发表时间:
2012-12
影响因子:
1.9
通讯作者:
Zhou,Jiying
Zhou,Jiying
中科院分区:
医学4区
文献类型:
--
作者:
Qin,Guangcheng;Fan,Xiaoping;Chen, Lixue;Shen,Chongbiao;Gui,Bei;Tan,Ge;Zhou,Jiying

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摘要目的:偏头痛是一种难治性疾病,是由于神经元过度兴奋,并具有高发病率,死亡率和残疾率。N-甲基-D-天冬氨酸受体2B(NR 2B)亚单位在偏头痛的发病机制中起重要作用。有证据表明,肿瘤抑制剂磷酸酶和张力蛋白同源物(PTEN)可以通过调节NR 2B水平对脑缺血损伤赋予神经保护作用。然而,PTEN在偏头痛中的作用仍不清楚。本研究旨在确定PTEN是否通过调节硝酸甘油诱导的偏头痛大鼠三叉神经节中的NR 2B、一氧化氮合酶(NOS)和一氧化氮(NO)参与偏头痛的发病机制。方法:将表达siPTEN或RFP的腺病毒分别注射到偏头痛大鼠的Sp 5(三叉神经脊束核)中。7天后,进行触觉感觉测试以检测触觉阈值。采用免疫荧光法、Western blot法、RT-PCR法和生化法检测偏头痛大鼠三叉神经节中PTEN、NR 2B、NOS和NO的含量。结果如下:用腺病毒表达的siPTEN预处理偏头痛大鼠,三叉神经节NR 2B、NOS和NO水平显著降低(P<0.05)。结论:这些结果表明,三叉神经节中的PTEN与偏头痛的发病机制有关,并且PTEN可能是未来通过调节NR 2B和减少三叉神经节中NO产生来治疗和/或预防偏头痛的一种新的且有前途的候选药物。
Abstract Objective: Migraine is a refractory disease that is due to neuronal hyperexcitability, and has high incidence, mortality, and disability rates. The N-methyl-D-aspartate receptor 2B (NR2B) subunit has been found to play an important role in the pathogenesis of migraine. There is evidence suggesting that a tumor suppressor phosphatase and tensin homolog (PTEN) can confer a neuroprotective effect on cerebral ischemic injury by regulating NR2B levels. However, the role of PTEN in migraines is still unclear. This study aimed to define whether PTEN is involved in the pathogenesis of migraine through modulating NR2B, nitric oxide synthase (NOS), and nitric oxide (NO) in the trigeminal ganglia of rats with glyceryl trinitrate-induced migraine. Methods: Adenovirus-expressing siPTEN or RFP was independently injected into the Sp5 (spinal trigeminal nucleus) of rats suffering from migraines. Seven days later, tactile sensory testing was performed to detect the tactile threshold. Immunofluorescence assay, western blot assay, RT-PCR, and biochemical examination were done to measure PTEN, NR2B, NOS, and NO levels in the trigeminal ganglia of migraine rats. Results: NR2B, NOS, and NO levels significantly (P<0·05) decreased in the trigeminal ganglia of migraine-affected rats pretreated with adenovirus-expressing siPTEN. Conclusion: These results suggest that PTEN in trigeminal ganglia is implicated in the pathogenesis of migraine, and PTEN may be a novel and promising candidate for future treatment and/or prevention of migraine via regulating NR2B and decreasing NO production in trigeminal ganglia.
DOI: 10.1016/j.mehy.2008.11.037
发表时间: 2009-05
期刊: Medical hypotheses
影响因子: 4.7
作者:
Ruidong Ye;X. Kong;Junliang L. Han;Gang Zhao
通讯作者: Ruidong Ye;X. Kong;Junliang L. Han;Gang Zhao
DOI: 10.1016/j.neuroscience.2007.10.048
发表时间: 2008-01-24
期刊: NEUROSCIENCE
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DOI: 10.1523/jneurosci.5449-03.2004
发表时间: 2004-04-21
影响因子: 5.3
作者:
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DOI: 10.2174/187152707781387233
发表时间: 2007-07
期刊: CNS & neurological disorders drug targets
影响因子: --
作者:
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通讯作者: L. Neeb;U. Reuter
DOI: 10.1124/jpet.106.117101
发表时间: 2007-05-01
影响因子: 3.5
作者:
Peeters, Magali;Gunthorpe, Martin J.;James, Michael F.
通讯作者: James, Michael F.