Dynamic expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor beta (PDGFRβ) in diabetic brain contributes to cognitive dysfunction

Background: Cognitive dysfunction is increasingly recognized as an important complication of diabetes mellitus (DM). Accumulating evidence indicates that the abnormality of cerebrovascular structure and function plays an essential role in diabetic cognitive impairment (DCI), however, changes in cerebrovascular factors have been blurred during the development of diabetes. Objective: To evaluate the changes in the structure and function of cerebrovascular in DCI mice and to investigate the changes of cerebral angiogenesis and stability factors during the development of DM. Methods: Diabetes was induced by feeding with high-fat diet combined with intraperitoneal injection of streptozotocin (STZ,120 mg/kg). Cognitive function was evaluated at different stages of DM, cerebral neovascularization, blood-brain barrier (BBB) permeability and hippocampal neurons were measured of DCI mice, and the expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor beta (PDGERB) in hippocampus was detected during the development of DM. Results: With the progress of diabetes, the learning and memory ability of mice gradually decreased, and DCI mice showed neuronal degeneration, increased BBB permeability and pathological cerebral neovascularization. Moreover, the expression of VEGF in the hippocampus increased first and then decreased at DM+8week, PDGFR beta decreased continuously with the development of diabetes. Conclusions: Our results demonstrate that DCI may be attributed to the dynamic expression of VEGF/PDGFR beta in diabetic hippocampus, and pathological cerebral neovascularization, increased BBB permeability and neuronal degeneration are the key links.