Nf2 Mutation in Schwann Cells Delays Functional Neural Recovery Following Injury.
Nf2 Mutation in Schwann Cells Delays Functional Neural Recovery Following Injury.
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DOI：
10.1016/j.neuroscience.2018.01.054
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发表时间：
2018-03-15
期刊：
影响因子：
3.3
通讯作者：
Hansen MR
中科院分区：
文献类型：
--
作者：
Truong K;Ahmad I;Jason Clark J;Seline A;Bertroche T;Mostaert B;Van Daele DJ;Hansen MR
Merlin是NF2肿瘤抑制基因的蛋白质产物。胚系NF2突变导致神经纤维瘤病2型(NF2)，以多发性颅内和脊髓神经鞘瘤为特征。NF2患者也经常出现周围神经病变。虽然Merlin在SC肿瘤形成中的作用已经得到了很好的证实，但它在SC动态平衡中的作用还不是很清楚。在这里，我们探讨了Merlin在SC对神经损伤的反应中的作用以及它们支持轴突再生的能力。我们在野生型(WT)和在干细胞中表达显性阴性Δ亚型的P0Sch NF239-121转基因小鼠身上进行了坐骨神经挤压。分别于伤后7、21、60、90d在压垫上测量平均接触爪面积，并于伤后90d进行神经传导测定，评价神经功能恢复情况。90d后取材，对轴突再生进行立体定量。用电子显微镜观察髓鞘超微结构。功能研究表明，与WT小鼠相比，Nf2突变小鼠的神经再生延迟。与WT小鼠相比，神经恢复延迟与突变体中再生轴突密度的降低和神经内膜间隙的增加有关。然而，WT和Nf2突变小鼠的功能和神经传导指标最终恢复到类似的水平，而Nf2突变小鼠再生轴突的百分比略有下降(~17%)。这些数据表明，Merlin在SCs中的功能除了在SC肿瘤中的作用外，还调节神经的超微结构，促进神经再生。
Merlin is the protein product of the NF2 tumor suppressor gene. Germline NF2 mutation leads to neurofibromatosis type 2 (NF2), characterized by multiple intracranial and spinal schwannomas. Patients with NF2 also frequently develop peripheral neuropathies. While the role of merlin in SC neoplasia is well established, its role in SC homeostasis is less defined. Here we explore the role of merlin in SC responses to nerve injury and their ability to support axon regeneration. We performed sciatic nerve crush in wild type (WT) and in P0SchΔ39-121 transgenic mice that express a dominant negative Nf2 isoform in SCs. Recovery of nerve function was assessed by measuring mean contact paw area on a pressure pad 7, 21, 60, and 90 days following nerve injury and by nerve conduction assays at 90 days following injury. After 90 days, the nerves were harvested and axon regeneration was quantified stereologically. Myelin ultrastructure was analyzed by electron microscopy. Functional studies showed delayed nerve regeneration in Nf2 mutant mice compared to the WT mice. Delayed neural recovery correlated with a reduced density of regenerated axons and increased endoneurial space in mutants compared to WT mice. Nevertheless, functional and nerve conduction measures ultimately recovered to similar levels in WT and Nf2 mutant mice, while there was a small (~17%) reduction in the percent of regenerated axons in the Nf2 mutant mice. The data suggest that merlin function in SCs regulates neural ultrastructure and facilitates neural regeneration, in addition to its role in SC neoplasia.
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影响因子：
3.5
作者：
Provenzano, Matthew J.;Minner, Sarah A.;Zander, Kaitlin;Clark, J. Jason;Kane, Catherine J.;Green, Steven H.;Hansen, Marlan R.
通讯作者：
Hansen, Marlan R.
影响因子：
4.7
作者：
Denisenko-Nehrbass, N;Goutebroze, L;Girault, JA
通讯作者：
Girault, JA
影响因子：
4.8
作者：
Lee, JH;Sundaram, V;Golubic, M
通讯作者：
Golubic, M
DOI：
10.1007/bf02427564
发表时间：
1998-04-01
期刊：
ITALIAN JOURNAL OF NEUROLOGICAL SCIENCES
影响因子：
--
作者：
Grazzi, L;Chiapparini, L;Bussone, G
通讯作者：
Bussone, G
影响因子：
12.7
作者：
Hagel, C;Lindenau, M;Mautner, VF
通讯作者：
Mautner, VF