p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation.
p75(NTR) expression and nuclear localization of p75(NTR) intracellular domain in spiral ganglion Schwann cells following deafness correlate with cell proliferation.
复制标题
DOI：
10.1016/j.mcn.2011.05.010
复制
发表时间：
2011-08
影响因子：
3.5
通讯作者：
Hansen, Marlan R.
中科院分区：
文献类型：
--
作者：
Provenzano, Matthew J.;Minner, Sarah A.;Zander, Kaitlin;Clark, J. Jason;Kane, Catherine J.;Green, Steven H.;Hansen, Marlan R.
螺旋神经节雪旺细胞（SGSC）为螺旋神经节神经元（SGN）提供髓鞘，是SGN神经营养支持的潜在来源。由于毛细胞的损失而导致的耳聋导致SGN的逐渐变性和死亡。维持或再生功能性听神经的成功努力可能取决于SGSC的健康群体，但SGSC对神经损伤的反应在很大程度上仍然未知。在这里，我们调查的作用，p75 NTR在SGSC反应逐渐去神经。耳聋后，与听力对照组相比，骨螺旋板（OSL）中的SGSC和随后的罗森塔尔管（RC）中的SGSC表达升高的p75 NTR。用S100和RIP抗体（雪旺细胞标记物）共标记p75 NTR阳性细胞，但不用抗神经丝标记。p75 NTR的表达模式反映了神经变性的模式，开始于耳蜗基底的OSL，后来延伸到顶端。SGSC表达分拣蛋白，一种前神经营养因子的p75 NTR共受体。神经生长因子前体（pro-NGF）和脑源性神经营养因子前体（pro-BDNF）均可诱导培养的SGSC凋亡。耳聋动物表现出显着更高的水平的SGSC增殖（通过BrdU摄取测量）相比，听力动物，而总的雪旺细胞密度保持稳定，表明SGSC增殖和细胞死亡的严格监管。经历细胞分裂的SGSC从细胞表面失去p75 NTR表达，并显示细胞内结构域（ICD）的核定位，提高了p75 NTR切割和ICD核定位调节SGSC增殖的可能性。这些结果表明，p75 NTR参与SGSC对耳聋和神经变性的反应。
Spiral ganglion Schwann cells (SGSCs) myelinate spiral ganglion neurons (SGNs) and represent a potential source of neurotrophic support for SGNs. Deafening due to loss of hair cells results in gradual degeneration and death of SGNs. Successful efforts to maintain or regenerate a functional auditory nerve may depend on a healthy population of SGSCs, yet the responses of SGSCs to neural injury remain largely unknown. Here we investigate the role of p75NTR in SGSC responses to gradual denervation. Following deafening, SGSCs in the osseous spiral lamina (OSL) and, subsequently, in Rosenthal's canal (RC) expressed elevated p75NTR compared to hearing controls. p75NTR-positive cells co-labeled with S100 and RIP antibodies (Schwann cell markers), but not with anti-neurofilament. The pattern of p75NTR expression mirrored the pattern of neural degeneration, beginning in the OSL of the cochlea base and later extending into the apex. SGSCs expressed sortilin, a p75NTR co-receptor for pro-neurotrophins. Both pro-nerve growth factor (pro-NGF) and pro-brain derived neurotrophic factor (proBDNF) induced apoptosis in cultured SGSCs. Deafened animals exhibited significantly higher levels of SGSC proliferation (as measured by BrdU uptake) compared to hearing animals while total Schwann cell density remained stable, suggesting a tight regulation of SGSC proliferation and cell death. SGSCs undergoing cell division lose p75NTR expression from the cell surface and demonstrate nuclear localization of the intracellular domain (ICD), raising the possibility that p75NTR cleavage and ICD nuclear localization regulate SGSC proliferation. These results suggest that p75NTR contributes to SGSC responses to deafening and neural degeneration.
登录
查看更多内容
影响因子：
2.5
作者：
Ferri, CC;Bisby, MA
通讯作者：
Bisby, MA
影响因子：
2.6
作者：
Provenzano, Matthew J.;Xu, Ningyong;Hansen, Marlan R.
通讯作者：
Hansen, Marlan R.
影响因子：
5.3
作者：
Harrington, AW;Kim, JY;Yoon, SO
通讯作者：
Yoon, SO
影响因子：
16.2
作者：
Pirvola, U;Ylikoski, J;Partanen, J
通讯作者：
Partanen, J
影响因子：
2.5
作者：
Gupta, R;Steward, O
通讯作者：
Steward, O