Dexmedetomidine Provides Protection Against Hippocampal Neuron Apoptosis and Cognitive Impairment in Mice with Alzheimer's Disease by Mediating the miR-129/YAP1/JAG1 Axis.

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 Aβ1-42-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 Aβ1-42-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 Aβ1-42-injected mice. In conclusion, the miR-129/YAP1/JAG1 axis could potentially be the mechanism by which Dex protects AD mice from cognitive impairment.