Gao Shangfeng, Fei Min, Cheng Chun, Yu Xiaowei, Chen Mengling, Shi Shuxian, Qin Jing, Guo Zhiqin, Shen Aiguo
The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
Neurochem Res. 2008 Jun;33(6):1090-100. doi: 10.1007/s11064-007-9555-y. Epub 2007 Dec 20.
Neuronal nitric oxide synthase (nNOS) has been implicated to influence peripheral nerve lesion and regeneration. Post-synaptic density-95 (PSD-95) is one of nNOS-anchoring proteins and plays an important role in specifying the sites of reaction of NO in nervous system. Here we established a rat sciatic nerve crush (SNC) model to examine the spatiotemporal expression of PSD-95 and nNOS. At gene levels, PSD-95 mRNA diminished shortly after crush, and significantly elevated from 2 days to 2 weeks, whereas nNOS decreased progressively post-operation, reached the valley at 1 day, and markedly up-regulated from 1 to 2 weeks after SNC. The expression of both molecules returned to the control level at 4 weeks post-injury. At protein levels, PSD-95 and nNOS underwent the similar changes as their gene expression except for a time lag during up-regulating. At their peak expression, PSD-95 co-labeled with nNOS in Schwann cells (SCs) of sciatic nerve within 0.5 mm from the lesion site, but had few colocalization in axons. In addition, the interaction between PSD-95 and nNOS enhanced significantly at 2 weeks after SNC. These results suggest a correlation of PSD-95 up-regulation with nNOS in reactive SCs of crushed sciatic nerve, which may lead to understanding the function of PSD-95 during peripheral nerve regeneration.
神经元型一氧化氮合酶(nNOS)被认为会影响周围神经损伤和再生。突触后致密蛋白95(PSD - 95)是nNOS的锚定蛋白之一,在确定神经系统中NO的反应位点方面发挥着重要作用。在此,我们建立了大鼠坐骨神经挤压伤(SNC)模型,以研究PSD - 95和nNOS的时空表达。在基因水平上,挤压伤后不久PSD - 95 mRNA减少,在2天至2周时显著升高,而nNOS在术后逐渐下降,在1天时达到谷底,在SNC后1至2周明显上调。损伤后4周,这两种分子的表达均恢复到对照水平。在蛋白质水平上,PSD - 95和nNOS的变化与其基因表达相似,只是上调过程中有时间滞后。在其表达峰值时,PSD - 95在距损伤部位0.5 mm内的坐骨神经雪旺细胞(SCs)中与nNOS共标记,但在轴突中的共定位很少。此外,SNC后2周,PSD - 95与nNOS之间的相互作用显著增强。这些结果表明,在挤压伤坐骨神经的反应性SCs中,PSD - 95上调与nNOS相关,这可能有助于理解PSD - 95在周围神经再生过程中的功能。