Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia
Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia
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DOI：
10.1002/cne.21537
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发表时间：
2008-01-10
影响因子：
2.5
通讯作者：
Gupta, Ranjan
中科院分区：
文献类型：
--
作者：
Chao, Tom;Pham, Khoa;Gupta, Ranjan
慢性神经压迫（CNC）损伤会引发损伤部位周围神经的一系列病理变化。然而，迄今为止，很少有人研究神经元细胞体对 CNC 损伤的反应。在这里，我们显示了损伤后 2 周和 1 个月，同侧 L4 和 L5 背根神经节 (DRG) 中的生长相关蛋白 43 (GAP-43) 优先上调，并且小直径降钙素基因相关蛋白 (CGRP) 和异凝集素 B4 (IB4) 阳性神经元对 Fluoro Ruby 的摄取增强。此外，CNC 损伤同侧的 L4 和 L5 DRG 也表现出神经丝 200 (NF-200) 神经元在早期时间点的显着减少以及 CGRP 和 1134 个神经元的增加。所有数字均归一化为与损伤后 6 个月评估 DRG 时的对照值相当的值。胶质源性神经营养因子 (GDNF) 蛋白的定量显示 L4 和 L5 DRG 上调，随后在损伤后的后期恢复到基线值。雪旺细胞对 GDNF 表达的上调在 I 个月受压坐骨神经标本的免疫组织化学和蛋白质印迹分析中也很明显。因此，CNC 诱导 DRG 发生表型变化，这种变化似乎与神经压缩损伤部位及其附近 GDNF 蛋白表达的增加暂时相关。
Chronic nerve compression (CNC) injury initiates a series of pathological changes within the peripheral nerve at the site of injury. However, to date, little work has been performed to explore neuronal cell body responses to CNC injury. Here we show a preferential upregulation of growth-associated protein-43 (GAP-43) and enhanced Fluoro Ruby uptake by the small-diameter calcitonin gene-related protein (CGRP) and isolectin B4 (IB4)-positive neurons in the L4 and L5 ipsilateral dorsal root ganglion (DRG) 2 weeks and I month post injury. Furthermore, L4 and L5 DRGs ipsilateral to CNC injury also demonstrated a marked reduction in neurofilament 200 (NF-200) neurons and an increase in CGRP and 1134 neurons at early time points. All numbers normalized to values comparable to those of control when the DRG was evaluated 6 months post injury. Quantification of glial-derived neurotrophic factor (GDNF) protein revealed an upregulation in L4 and L5 DRG followed by a return to baseline values at later stages following injury. Upregulation of GDNF expression by Schwann cells was also readily apparent with both immunobistochemistry and Western blot analysis of I month compressed sciatic nerve specimens. Thus, CNC induces a phenotypic change in the DRG that appears to be temporally associated with increases in GDNF protein expression at and near the site of the compression injury in the nerve.