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大鼠肾动脉闭塞后胸腰段脊髓神经元和背根神经节中CREB的磷酸化

Phosphorylation of CREB in thoracolumbar spinal neurons and dorsal root ganglia after renal artery occlusion in rat.

作者信息

Lishnak T S, Vizzard M A

机构信息

Department of Neurology, College of Medicine, University of Vermont, Burlington 05405, USA.

出版信息

Auton Neurosci. 2001 Dec 10;94(1-2):62-73. doi: 10.1016/S1566-0702(01)00346-0.

DOI:10.1016/S1566-0702(01)00346-0
PMID:11775709
Abstract

These studies have demonstrated that ipsilateral renal artery occlusion (RAO) in rat results in the phosphorylation of cyclic AMP (cAMP) response element binding protein (p-CREB) in the thoracolumbar (T8-L2) spinal cord and associated dorsal root ganglia (DRG). p-CREB-immunoreactivity (IR) was expressed bilaterally in the thoracolumbar spinal cord, whereas expression in the DRG was ipsilateral relative to RAO. p-CREB-IR was primarily expressed in four distinct regions of the spinal cord: medial or lateral dorsal horn (MDH or LDH), dorsal commissural nucleus (DCN) and the region of the intermediolateral cell column (IML). After RAO, p-CREB-IR was greatest in the T13-L2 spinal segments. Within the T13-L1 spinal segments, p-CREB-IR was greatest in the MDH, LDH and DCN and expression in each of these regions was comparable within a segment. Following RAO, there was a significant (p < or = 0.001) increase in the percentage (86-98%) of p-CREB-IR spinal neurons expressing choline acetyltransferase (ChAT)-IR (a marker of preganglionic neurons) in the IML of the T10, T12 and L1 spinal segments examined. After ipsilateral RAO, expression of p-CREB-IR was increased in the ipsilateral, T8-L2 DRG with the greatest number of p-CREB-IR dorsal root ganglion cells being located in the L1 dorsal root ganglion. Retrograde tracing with Fluorogold (FG) to label renal afferent cells in the DRG revealed a significant (p < or = 0.01) increase in the percentage (75-86%) of renal afferent cells expressing p-CREB-IR after ipsilateral RAO. These studies demonstrate that p-CREB-IR is a useful tool for examining the distribution of spinal neurons and DRG involved in reflexes of renal origin. In addition, expression of p-CREB-IR may be coupled to late response genes that may exert long-term changes in neuronal function after RAO.

摘要

这些研究表明,大鼠的同侧肾动脉闭塞(RAO)会导致胸腰段(T8-L2)脊髓和相关背根神经节(DRG)中环状AMP(cAMP)反应元件结合蛋白(p-CREB)的磷酸化。p-CREB免疫反应性(IR)在胸腰段脊髓双侧表达,而在DRG中的表达相对于RAO是同侧的。p-CREB-IR主要在脊髓的四个不同区域表达:内侧或外侧背角(MDH或LDH)、背连合核(DCN)和中间外侧细胞柱(IML)区域。RAO后,p-CREB-IR在T13-L2脊髓节段中最为明显。在T13-L1脊髓节段内,p-CREB-IR在MDH、LDH和DCN中最为明显,且每个区域在一个节段内的表达相当。RAO后,在检查的T10、T12和L1脊髓节段的IML中,表达胆碱乙酰转移酶(ChAT)-IR(节前神经元的标志物)的p-CREB-IR脊髓神经元百分比显著(p≤0.001)增加(86-98%)。同侧RAO后,同侧T8-L2 DRG中p-CREB-IR的表达增加,p-CREB-IR背根神经节细胞数量最多的位于L1背根神经节。用荧光金(FG)进行逆行追踪以标记DRG中的肾传入细胞,结果显示同侧RAO后表达p-CREB-IR的肾传入细胞百分比显著(p≤0.01)增加(75-86%)。这些研究表明,p-CREB-IR是检查参与肾源性反射的脊髓神经元和DRG分布的有用工具。此外,p-CREB-IR的表达可能与晚期反应基因相关,这些基因可能在RAO后对神经元功能产生长期变化。

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