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Changes in VGLUTI and VGLUT2 expression in rat dorsal root ganglia and spinal cord following spared nerve injury

机译:神经损伤后大鼠背根神经节和脊髓中VGLUTI和VGLUT2表达的变化

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摘要

Disturbance of glutamate homeostasis is a well-characterized mechanism of neuropathic pain. Vesicular glutamate transporters (VGLUTs) determine glutamate accumulation in synaptic vesicles and their roles in neuropathic pain have been suggested by gene-knockout studies. Here, we investigated the spatio-temporal changes in VGLUT expression during the development of neuropathic pain in wild-type rats. Spared nerve injury (SNI) induced mechanical allodynia from postoperative day 1 to at least day 14. Expression of VGLUT1 and VGLUT2 in dorsal root ganglia and spinal cord was examined by western blot analyses on different postoperative days. We observed that VGLUT2 were selectively upregulated in crude vesicle fractions from the ipsilateral lumbar enlargement on postoperative days 7 and 14, while VGLUT1 was transiently downregulated in ipsilateral DRG (day 4) and contralateral lumbar enlargement (day 1). Upregulation of VGLUT2 was not accompanied by alterations in vesicular expression of synaptotagmin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Thus, VGLUTs expression, especially VGLUT2, is regulated following peripheral nerve injury. Temporal regulation of VGLUT2 expression in spinal cord may represent a novel presynaptic mechanism contributing to injury-induced glutamate imbalance and associated neuropathic pain. (C) 2016 Elsevier Ltd. All rights reserved.
机译:谷氨酸稳态的紊乱是神经性疼痛的一个公认的机制。基因敲除研究表明,囊泡的谷氨酸转运蛋白(VGLUTs)决定了谷氨酸在突触小泡中的蓄积,它们在神经性疼痛中的作用已被提出。在这里,我们调查了野生型大鼠神经性疼痛的发展过程中VGLUT表达的时空变化。术后第1天至至少第14天,稀有神经损伤(SNI)引起机械性异常性疼痛,并在术后不同天用Western blot分析了VGLUT1和VGLUT2在背根神经节和脊髓中的表达。我们观察到,术后第7和14天,来自同侧腰部增大的粗小囊泡部分中VGLUT2选择性上调,而同侧DRG(第4天)和对侧腰部增大(第1天)中VGLUT1瞬时下调。 VGLUT2的上调不伴有突触标记素或3磷酸甘油醛脱氢酶(GAPDH)的囊泡表达变化。因此,在周围神经损伤后,VGLUT的表达,特别是VGLUT2,受到调节。脊髓中VGLUT2表达的时间调控可能代表了一种新的突触前机制,可导致损伤引起的谷氨酸失衡和相关的神经性疼痛。 (C)2016 Elsevier Ltd.保留所有权利。

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