Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Eur J Neurosci. 2022 Mar;55(6):1471-1482. doi: 10.1111/ejn.15635. Epub 2022 Mar 10.
Obstructive sleep apnoea syndrome (OSAS) is a potentially severe sleep disorder characterized by intermittent hypoxia, and there is growing evidence that OSAS can lead to cognitive decline. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) plays a key role in synaptic plasticity. We established CIH model in male SD rats and examined their expression of p-ERK1/2 and PSD-95, as well as in CIH group; the effect of SL327 on the expression of p-ERK1/2 and PSD-95 in hippocampus of CIH model rats was observed by pretreating the experimental rats with SL327 during peak time of p-ERK1/2 expression. Mean oxygen saturation in the tail artery was lower in the CIH group. CIH groups exhibited increased escape latencies in the navigation test and decreased numbers of platform crossings in the space exploration test. Reduced volume, irregular structure, deepened cytoplasmic eosinophilic staining in the cytoplasm and decreased nuclear size were found in hippocampal neurons in the 28-d CIH and 28-d CIH + SL327 group. The hippocampus of CIH rats' p-ERK expressions gradually increased with prolonged CIH exposure but decreased after SL327 treatment. Moreover, PSD-95 expressions gradually reduced in the 14-d CIH, 21-d CIH and 28-d CIH groups but increased in the SL327-treated group. The SL327 intervention decreased p-ERK1/2 expression, increased PSD-95 expression and improved cognitive function in CIH rats. The present findings provide some insights into the mechanisms underlying OSAS-associated cognitive impairment.
阻塞性睡眠呼吸暂停综合征（OSAS）是一种潜在的严重睡眠障碍，其特征是间歇性缺氧，越来越多的证据表明 OSAS 可导致认知功能下降。细胞外信号调节激酶 1/2（ERK1/2）在突触可塑性中发挥关键作用。我们建立了雄性 SD 大鼠的 CIH 模型，并检测了其 p-ERK1/2 和 PSD-95 的表达，以及在 CIH 组中；在 p-ERK1/2 表达高峰时，用 SL327 预处理实验大鼠，观察 SL327 对 CIH 模型大鼠海马 p-ERK1/2 和 PSD-95 表达的影响。尾动脉平均氧饱和度在 CIH 组较低。CIH 组在导航测试中表现出潜伏期延长，在空间探索测试中穿越平台的次数减少。在 28 天 CIH 和 28 天 CIH+SL327 组中，海马神经元的体积减小，结构不规则，胞质嗜酸性染色加深，核大小减小。随着 CIH 暴露时间的延长，CIH 大鼠海马 p-ERK 表达逐渐增加，但经 SL327 处理后降低。此外，14 天 CIH、21 天 CIH 和 28 天 CIH 组 PSD-95 表达逐渐减少，而 SL327 处理组表达增加。SL327 干预降低了 p-ERK1/2 的表达，增加了 PSD-95 的表达，改善了 CIH 大鼠的认知功能。这些发现为 OSAS 相关认知障碍的机制提供了一些见解。
