Anterograde transport of tumor necrosis factor-α in the intact and injured rat sciatic nerve
Anterograde transport of tumor necrosis factor-α in the intact and injured rat sciatic nerve
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DOI：
10.1523/jneurosci.22-02-00536.2002
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发表时间：
2002-01-15
影响因子：
5.3
通讯作者：
Sommer, C
中科院分区：
文献类型：
--
作者：
Schäfers, M;Geis, C;Sommer, C
肿瘤坏死因子-α (TNF) 在中枢和外周末端在周围神经损伤后的早期退行性病理学和疼痛行为中发挥着关键作用。最近的研究表明，TNF 可能通过轴突运输，从而有助于这些中枢和外周作用。为了表征这种运输，我们使用了区分顺行和逆行流的双重结扎（DL）程序，以可视化与神经营养蛋白神经生长因子（NGF）和神经肽降钙素基因相关肽（CGRP）相比的内源性TNF的轴突运输。在完整神经中，TNF 和 CGRP 免疫反应性主要聚集在 DL 附近（顺行转运），而 NGF 则表现出唯一的逆行转运。慢性缩窄性损伤 (CCl) 后 20 小时，TNF 和 CGRP 向神经损伤部位的顺行转运显着增加。通过外源应用的 I-125-TNF 和 I-125-NGF 的轴突转运分析证实了结果。神经内注射后，I-125-TNF 在 DL 附近积聚，表明顺行转运。在未结扎的神经中，I-125-TNF 特异地顺行转运至受神经支配的肌肉，但不转运至皮肤。 CCl后，I-125-TNF在周围神经损伤部位附近积聚，并且内源性TNF仅在中型和大型背根神经节（DRG）神经元中增加，表明DRG神经元是受伤坐骨神经中TNF流量增加的主要来源。我们的结果表明，TNF 的顺行转运在细胞体远端周围神经损伤的早期神经元反应中发挥着重要作用。
Tumor necrosis factor-alpha (TNF) appears as a key player at both central and peripheral terminals in early degenerative pathology and pain behavior after peripheral nerve injury. Recent studies suggest that TNF may be axonally transported and thereby contribute to these central and peripheral actions. To characterize this transport, we used a double ligation (DL) procedure that distinguishes between anterograde and retrograde flow to visualize the axonal transport of endogenous TNF compared with the neurotrophin nerve growth factor (NGF) and to the neuropeptide calcitonin gene-related peptide (CGRP). In the intact nerve, TNF and CGRP immunoreactivity predominantly accumulated proximal to the DL (anterograde transport), whereas NGF displayed exclusive retrograde transport. At 20 hr after chronic constrictive injury (CCl), the anterograde transport of TNF and CGRP to the nerve injury site was dramatically increased. The results were corroborated by the analysis of axonal transport of exogenously applied I-125-TNF and I-125-NGF. After intraneural injection, I-125-TNF accumulated proximally to a DL, suggesting anterograde transport. In the unligated nerve, I-125-TNF was specifically transported anterogradely to the innervated muscle but not to skin. After CCl, I-125-TNF accumulated proximally to the peripheral nerve injury site, and endogenous TNF was exclusively increased in medium-sized and large dorsal root ganglion (DRG) neurons, suggesting that DRG neurons are a major contributing source of increased TNF traffic in the injured sciatic nerve. Our results suggest that anterograde transport of TNF plays a major role in the early neuronal response to peripheral nerve injury at sites distal to the cell body.