SNAP-25 Contributes to Neuropathic Pain by Regulation of VGLuT2 Expression in Rats
SNAP-25 Contributes to Neuropathic Pain by Regulation of VGLuT2 Expression in Rats
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SNAP-25 通过调节大鼠 VGLuT2 表达导致神经性疼痛
DOI：
10.1016/j.neuroscience.2019.10.007
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发表时间：
2019-11
期刊：
影响因子：
3.3
通讯作者：
Zou Wangyuan
中科院分区：
文献类型：
--
作者：
Wang Jiang;Xu Wei;Kong Yan;Huang Jiangju;Ding Zhuofeng;Deng Meiling;Guo Qulian;Zou Wangyuan
突触体相关蛋白25（SNAP-25）在神经病理性疼痛中起重要作用。然而，基本的机制在很大程度上是未知的。囊泡谷氨酸转运体2（VGluT 2）是囊泡谷氨酸转运体的一种亚型，其控制谷氨酸的储存和释放。在本研究中，我们发现VGluT 2的表达水平与SNAP-25的上调在大鼠脊髓慢性压迫性损伤（CCI）诱导的神经病理性疼痛。通过肉毒毒素A（BoNT/A）切割SNAP-25减弱机械性异常性疼痛，下调VGluT 2的表达并减少谷氨酸释放。过表达VGluT 2可阻断BoNT/A的镇痛作用。SNAP-25在未处理大鼠中的上调增加了VGluT 2表达并诱导了疼痛反应行为。在嗜铬细胞瘤（PC 12）细胞中，VGluT 2的表达也依赖于SNAP-25的失调。此外，我们发现VGluT 2参与了SNAP-25介导的星形胶质细胞表达的调节，并且PKA/p-CREB通路的激活介导了神经病理性疼痛中SNAP-25的上调。我们的研究结果表明，VGluT 2有助于SNAP-25在维持神经病理性疼痛的发展中的作用，并提出了SNAP-25调节神经病理性疼痛的新机制。
Synaptosomal-associated protein 25 (SNAP-25) plays an important role in neuropathic pain. However, the underlying mechanism is largely unknown. Vesicular glutamate transporter 2 (VGluT2) is an isoform of vesicular glutamate transporters that controls the storage and release of glutamate. In the present study, we found the expression levels of VGluT2 correlated with the upregulation of SNAP-25 in the spinal cord of rats following chronic constriction injury (CCI)-induced neuropathic pain. Cleavage of SNAP-25 by Botulinum toxin A (BoNT/A) attenuated mechanical allodynia, downregulated the expression of VGluT2 and reduced glutamate release. Overexpression of VGluT2 abolished the antinociceptive effect of BoNT/A. Upregulation of SNAP-25 in naive rats increased VGluT2 expression and induced pain-responsive behaviors. In pheochromocytoma (PC12) cells, the expression of VGluT2 was also depended on SNAP-25 dysregulation. Moreover, we found VGluT2 was involved in SNAP-25-mediated regulation of astrocyte expression and activation of the PKA/p-CREB pathway mediated the upregulation of SNAP-25 in neuropathic pain. The findings of our study indicate that VGluT2 contributes to the effect of SNAP-25 in maintaining the development of neuropathic pain and suggests a novel mechanism underlying SNAP-25 regulation of neuropathic pain.
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影响因子：
2.5
作者：
R. Sun;Y. Tu;N. Lawand;Jing-Yin Yan;Q. Lin;W. Willis
通讯作者：
R. Sun;Y. Tu;N. Lawand;Jing-Yin Yan;Q. Lin;W. Willis
影响因子：
15.1
作者：
Loram, Lisa C.;Taylor, Frederick R.;Strand, Keith A.;Harrison, Jacqueline A.;RzasaLynn, Rachael;Sholar, Paige;Rieger, Jayson;Maier, Steven F.;Watkins, Linda R.
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影响因子：
6.4
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通讯作者：
Levenson, R. M.
影响因子：
2.5
作者：
Alvarez, FJ;Villalba, RM;Schneider, SP
通讯作者：
Schneider, SP
影响因子：
3.5
作者：
Azogu, Idu;Plamondon, Helene
通讯作者：
Plamondon, Helene