Proteomic analysis by 4D label-free MS-PRM identified that Nptx1, Ptpmt1, Slc25a11, and Cpt1c are involved in diabetes-associated cognitive dysfunction

Diabetes-associated cognitive dysfunction (DACD) is a chronic ailment that exerts a substantial influence on the overall well-being of individuals. The hippocampus assumes a pivotal role in the progression and sustenance of cognitive impairment. The identification of differentially expressed proteins (DEPs) in the hippocampus is crucial for understanding the mechanisms of DACD. A rat model of DACD was established by a high-fat diet combined with streptozotocin intraperitoneal injection. The Morris water maze (MWM), hematoxylin and eosin (H&E) staining, Nissl staining, and transmission electron microscope (TEM) were performed on the rats. The proteins expressed in the hippocampus were detected using 4D label-free quantitative proteomics. Four DEPs, namely Nptx1, Ptpmt1, Slc25a11, and Cpt1c, were validated using parallel reaction monitoring (PRM). Our study found that hippocampal lesions were present in the DACD rat models. There were 59 up-regulated and 98 down-regulated DEPs in the Model group compared to the Control group. We found that the levels of Nptx1, Ptpmt1, Slc25a11, and Cpt1c were elevated in the Model group, which are important for cell mitochondrial function. It should be noted that in our study, we only used PRM to validate the expression of these proteins. However, more evidence is needed to establish the relationship between these protein changes and DACD. Our research results may provide further insight into the molecular pathology of hippocampal injury in DACD. In addition, further studies and clinical trials are required to confirm our findings and establish a more conclusive molecular mechanism for DACD.