Trelagliptin relieved cognitive impairment of diabetes mellitus rats: Involvement of PI3K/Akt/GSK-3β and inflammation pathway

作者：Min Lei, Xiying Guo, Yue Yao, Ting Shu, Zhanhong Ren, Xiaosong Yang, Changhan Ouyang, Qingjie Chen, Chao Liu, Xiufen Liu · 发表于：Experimental Gerontology · 年份：2023 · DOI：10.1016/j.exger.2023.112307 · 被引用次数：17 · 研究领域：Alzheimer's disease research and treatments、Neuropeptides and Animal Physiology、Neuroinflammation and Neurodegeneration Mechanisms

Cognitive impairment frequently coexists with diabetes. Trelagliptin is a once-weekly taking selective dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-term effective hypoglycemic medicine; nonetheless, its effects for the treatment of diabetes-related cognitive impairment have only sometimes been explored. In this study, a DM model was built using streptozotocin (STZ) and a high-fat diet (HFD). The morris water maze test on DM rats revealed a considerably reduced capacity for spatial learning and memory, but trelagliptin was able to restore function. Trelagliptin could lower the mRNA expression of inflammatory factors such IL-1β, TNF-α, and IL-6 in DM rats. It could also reduce the ratio of p-IKKα/IKKα, and the immunofluorescence result of NF-κB also demonstrated a drop. Trelagliptin partially restored dendritic spines and prevented the loss or shrinkage of neurons, respectively, according to the results of Nissl's staining and golgi staining. Furthermore, PI3K/Akt/GSK-3β has been activated, and synaptic plasticity has been modified during this process. In conclusion, trelagliptin improved the cognitive lesion in DM rats by suppressing the activation of the inflammatory route and by activating the PI3K/Akt/GSK-3β pathway at the same time, as well as interacting with the pathways that protect neurons, which still need further research.