Department of Regenerative Medicine, College of Pharmacy, Jilin University, Changchun, Jilin, 130021, China.
Laboratory of Cancer Precision Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Sci Rep. 2024 Nov 6;14(1):26909. doi: 10.1038/s41598-024-78169-w.
High altitude is characterized by low oxygen, low pressure, and high radiation. When migrates from low to high altitudes, the body's tissues and organs experience hypoxic stress and will present acoustic adaptation as the protective response. However, the mechanisms of acoustic adaptation at high altitudes remain unclear. In this study, cochlear tissues from Wistar rats were collected at 15, 30, 60, 120, and 180 days after high-altitude migration. Transcriptome sequencing was conducted and DESeq algorithm revealed expression patterns of Differentially Expressed Genes(DEGs) after high altitude migration. Day 60 is a critical stage for cochlear tissue "damage" and "repair" in high-altitude conditions. Transmission Electron Microscopy (TEM) observations of structures also support the findings. A time-series gene co-expression network algorithm was used to investigate gene regulatory patterns and key genes after migration. Immunofluorescence, immunohistochemistry, and qPCR were per-formed for key gene validation and localization. At Day 60, the peak DEG count occurs in rats migrating to high altitude, aligning with the critical phase for cochlear tissue damage and repair at high altitudes. Repair hinges on synaptic plasticity and myelination-linked processes, influencing modules M4 to M6. Module M4's activation gradually diminishes from its peak. However, the 'damage' effect is orchestrated by inflammation-related processes in modules M3 to M5, with module M3's activation also waning. Key gene module M4, pivotal for repair during this pivotal phase, encompasses Sptbn5, Cldn1, Gfra2, and Lims2 as its core genes. Immunohistochemistry reveals Sptbn5's presence in cochlear neurons, hair cells, Schwann cells and stria vascularis tissue. Cldn1 and Gfra2 predominantly localize within the cochlear neuron region. These results may suggest new directions for future research on acoustic acclimatization to high altitude.
高海拔地区的特点是低氧、低压和高辐射。当从低海拔地区迁移到高海拔地区时，身体的组织和器官会经历缺氧应激，并会出现声适应作为保护反应。然而，高海拔地区声适应的机制尚不清楚。在这项研究中，从高海拔迁移后 15、30、60、120 和 180 天的 Wistar 大鼠收集耳蜗组织。进行转录组测序，DESeq 算法揭示了高海拔迁移后差异表达基因 (DEGs) 的表达模式。第 60 天是高海拔条件下耳蜗组织“损伤”和“修复”的关键阶段。结构的透射电子显微镜 (TEM) 观察也支持了这一发现。使用时间序列基因共表达网络算法研究迁移后的基因调控模式和关键基因。进行免疫荧光、免疫组织化学和 qPCR 以验证和定位关键基因。在第 60 天，迁移到高海拔的大鼠中出现了 DEG 计数的峰值，与高海拔条件下耳蜗组织损伤和修复的关键阶段一致。修复取决于突触可塑性和髓鞘化相关过程，影响模块 M4 到 M6。模块 M4 的激活逐渐从峰值减弱。然而，模块 M3 到 M5 中的炎症相关过程协调了“损伤”效应，模块 M3 的激活也在减弱。关键基因模块 M4 是这个关键阶段修复的核心，其核心基因包括 Sptbn5、Cldn1、Gfra2 和 Lims2。免疫组织化学显示 Sptbn5 存在于耳蜗神经元、毛细胞、施万细胞和血管纹组织中。Cldn1 和 Gfra2 主要定位于耳蜗神经元区域。这些结果可能为未来研究高海拔声适应提供新的方向。
