Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, 210096, China.
Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, Southeast University, Nanjing, 210096, China.
Sci Rep. 2017 Jun 14;7(1):3506. doi: 10.1038/s41598-017-03810-w.
SGNs are the primary auditory neurons, and damage or loss of SGNs leads to sensorineural hearing loss. BMP4 is a growth factor that belongs to the TGF-β superfamily and has been shown to play a key role during development, but little is known about its effect on postnatal cochlear SGNs in mice. In this study, we used the P3 Bhlhb5-cre/tdTomato transgenic mouse model and FACS to isolate a pure population of Bhlhb5+ SGNs. We found that BMP4 significantly promoted SGN survival after 7 days of culture. We observed fewer apoptotic cells and decreased expression of pro-apoptotic marker genes after BMP4 treatment. We also found that BMP4 promoted monopolar neurite outgrowth of isolated SGNs, and high concentrations of BMP4 preserved the number and the length of neurites in the explant culture of the modiolus harboring the SGNs. We showed that high concentration of BMP4 enhanced neurite growth as determined by the higher average number of filopodia and the larger area of the growth cone. Finally, we found that high concentrations of BMP4 significantly elevated the synapse density of SGNs in explant culture. Thus, our findings suggest that BMP4 has the potential to promote the survival and preserve the structure of SGNs.
SGNs 是主要的听觉神经元，SGNs 的损伤或丢失会导致感音神经性听力损失。BMP4 是一种生长因子，属于 TGF-β 超家族，已被证明在发育过程中发挥关键作用，但对其在小鼠出生后耳蜗 SGNs 中的作用知之甚少。在这项研究中，我们使用了 P3 Bhlhb5-cre/tdTomato 转基因小鼠模型和 FACS 来分离纯的 Bhlhb5+ SGNs 群体。我们发现 BMP4 可显著促进培养 7 天后 SGN 的存活。BMP4 处理后，凋亡细胞减少，促凋亡标志物基因的表达降低。我们还发现 BMP4 促进了分离的 SGN 中单极轴突的生长，高浓度的 BMP4 可保留含有 SGN 的耳蜗蜗轴外植体培养中神经元的数量和长度。我们表明，高浓度的 BMP4 通过增加丝状伪足的平均数量和生长锥的面积来增强神经突的生长。最后，我们发现高浓度的 BMP4 可显著提高 SGN 在体外培养中的突触密度。因此，我们的研究结果表明，BMP4 具有促进 SGN 存活和维持结构的潜力。
