Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease that leads to progressive cognitive, memory, and learning dysfunction that affects the aging population. Dexmedetomidine (Dex) might be beneficial for postoperative cognitive function in elderly patients. However, the exact mechanism underlying the protective role of Dex against cognitive impairment requires further elucidation. The present study aims to determine whether miR-129 is involved in the protective effect of Dex against Aβ_1–42-induced hippocampal neuron apoptosis and cognitive impairment in mice. In our study, Y-shaped maze and water maze tests were conducted to evaluate the cognitive function of AD mice, while neuronal apoptosis was measured by Terminal Deoxynucleotidyl Transferase–Mediated dUTP Nick-End Labeling (TUNEL) staining. The findings showed that Dex administration resulted in the enhancement of miR-129 expression with declined hippocampal neuron apoptosis and attenuated cognitive impairment in Aβ_1–42-injected mice. miR-129 targeted YAP1 and disrupted its interaction with JAG1, leading to a decline in hippocampal neuron apoptosis and attenuated cognitive impairment in Aβ_1–42-injected mice. In conclusion, the miR-129/YAP1/JAG1 axis could potentially be the mechanism by which Dex protects AD mice from cognitive impairment.

阿尔茨海默氏病（AD）是一种多因素神经退行性疾病，会导致进行性认知，记忆和学习功能障碍，从而影响人口老龄化。右美托咪定（Dex）可能对老年患者的术后认知功能有益。然而，Dex对抗认知障碍的保护作用的确切机制需要进一步阐明。本研究旨在确定miR-129是否参与Dex对_Aβ1–42的保护作用诱导的小鼠海马神经元凋亡和认知障碍。在我们的研究中，进行了Y型迷宫和水迷宫测试，以评估AD小鼠的认知功能，同时通过末端脱氧核苷酸转移酶介导的dUTP尼克末端标记（TUNEL）染色来测量神经元的凋亡。研究结果表明，在注射_Aβ1–42的小鼠中，Dex给药可导致miR-129表达增强，海马神经元凋亡减少，认知功能减退。miR-129靶向YAP1并破坏了其与JAG1的相互作用，导致海马神经元凋亡减少，_Aβ1–42的认知障碍减弱注射的小鼠。总之，miR-129 / YAP1 / JAG1轴可能是Dex保护AD小鼠免受认知障碍的机制。