SUN-194 - Cognitive Impairment in Type 2 Diabetes Mellitus via the PRLR/JAK2/STAT5 Signaling Pathway

Objective: Cognitive impairment is closely associated with T2D, its underlying mechanisms is to be further clarified in this study.

Methods: In this study, a streptozotocin (STZ)-induced T2D mouse model was used to perform the Morris water maze test. Hematoxylin-eosin (HE) staining was applied to examine structural changes in the hippocampus. Transcriptomic analysis was conducted on hippocampal tissue,immunohistochemical staining was used to detect the inflammatory cytokines IL-1ßand IL-6.RT-PCR and Western blotting were performed respectively.

Results: T2D mice exhibited significant cognitive impairment, as evidenced in the spatial probe trial of the Morris water maze by prolonged escape latency, reduced time spent in the original platform quadrant, and disorganized swimming trajectories (all p< 0.05). Transcriptomic analysis identified 298 differentially expressed genes between the two groups, including 139 upregulated and 159 downregulated genes, and KEGG pathway analysis indicated upregulation of the prolactin signaling pathway. Compared with the control group, the hippocampal tissue of mice in the T2D group exhibited marked morphological changes, such as nuclear pyknosis. Levels of IL-1ß and IL-6 were increased (p? 0.05), and the expression of key proteins in the prolactin signaling pathway-PRLR, p-JAK2/JAK2, and p-STAT5/STAT5-was significantly upregulated.

Conclusion: T2D may lead to cognitive impairment via activation of the PRLR/JAK2/STAT5 signaling pathway, providingnew insight into the prolactin signaling pathway underlying T2D-associated cognitive dysfunction.