Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination.
Axonal neuregulin 1 is a rate limiting but not essential factor for nerve remyelination.
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DOI：
10.1093/brain/awt148
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Bennett DL
中科院分区：
文献类型：
--
作者：
Fricker FR;Antunes-Martins A;Galino J;Paramsothy R;La Russa F;Perkins J;Goldberg R;Brelstaff J;Zhu N;McMahon SB;Orengo C;Garratt AN;Birchmeier C;Bennett DL
神经调节蛋白1作为轴突信号调节许旺细胞发育的多个方面，包括许旺细胞前体的存活和迁移、轴突的鞘化和随后的髓鞘的加工。为了研究该因子在神经损伤后髓鞘再生和修复中的作用，我们使用他莫昔芬诱导型Cre重组酶转基因小鼠系统消融了成人神经系统中的neuregulin 1。神经调节蛋白1的丢失损害神经挤压后的髓鞘再生，但不影响与沃勒变性或轴突再生相关的许旺细胞增殖或巨噬细胞对髓鞘碎片的清除。髓鞘形成的变化在伤后10天最明显，但在挤压后2个月仍然明显。转录分析表明，在缺乏神经调节蛋白1的动物神经修复过程中，髓鞘相关基因的表达减少。我们还研究了在更严重的损伤模型中，坐骨神经横断和再吻合的长期修复。在neuregulin 1突变小鼠中，神经切断和再吻合后2个月，髓鞘再生再次受损。然而，到损伤后3个月，缺乏神经调节蛋白1的轴突有效地重新髓鞘化，并且与对照组几乎没有区别。因此，神经调节蛋白1信号传导是神经修复的重要因素，调节损伤后早期的髓鞘再生和功能恢复速率。然而，与发育相反，神经损伤后髓鞘形成的决定并不依赖于轴突神经调节蛋白1的表达。因此，在损伤后的早期阶段，轴突神经调节蛋白1促进神经修复，但在晚期阶段，其他信号通路似乎进行补偿。
Neuregulin 1 acts as an axonal signal that regulates multiple aspects of Schwann cell development including the survival and migration of Schwann cell precursors, the ensheathment of axons and subsequent elaboration of the myelin sheath. To examine the role of this factor in remyelination and repair following nerve injury, we ablated neuregulin 1 in the adult nervous system using a tamoxifen inducible Cre recombinase transgenic mouse system. The loss of neuregulin 1 impaired remyelination after nerve crush, but did not affect Schwann cell proliferation associated with Wallerian degeneration or axon regeneration or the clearance of myelin debris by macrophages. Myelination changes were most marked at 10 days after injury but still apparent at 2 months post-crush. Transcriptional analysis demonstrated reduced expression of myelin-related genes during nerve repair in animals lacking neuregulin 1. We also studied repair over a prolonged time course in a more severe injury model, sciatic nerve transection and reanastamosis. In the neuregulin 1 mutant mice, remyelination was again impaired 2 months after nerve transection and reanastamosis. However, by 3 months post-injury axons lacking neuregulin 1 were effectively remyelinated and virtually indistinguishable from control. Neuregulin 1 signalling is therefore an important factor in nerve repair regulating the rate of remyelination and functional recovery at early phases following injury. In contrast to development, however, the determination of myelination fate following nerve injury is not dependent on axonal neuregulin 1 expression. In the early phase following injury, axonal neuregulin 1 therefore promotes nerve repair, but at late stages other signalling pathways appear to compensate.
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影响因子：
16.2
作者：
Brinkmann, Bastian G.;Agarwal, Amit;Sereda, Michael W.;Garratt, Alistair N.;Mueller, Thomas;Wende, Hagen;Stassart, Ruth M.;Nawaz, Schanila;Humml, Christian;Velanac, Viktorija;Radyushkin, Konstantin;Goebbels, Sandra;Fischer, Tobias M.;Franklin, Robin J.;Lai, Cary;Ehrenreich, Hannelore;Birchmeier, Carmen;Schwab, Markus H.;Nave, Klaus Armin
通讯作者：
Nave, Klaus Armin
影响因子：
5.3
作者：
Chen, S;Velardez, MO;Corfas, G
通讯作者：
Corfas, G
影响因子：
6.2
作者：
Birchmeier, Carmen;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
4.2
作者：
Chen, LE;Liu, K;Urbaniak, JR
通讯作者：
Urbaniak, JR
影响因子：
4.2
作者：
COHEN, JA;YACHNIS, AT;SCHERER, SS
通讯作者：
SCHERER, SS