Expression of cAMP responsive element binding protein and β-amyloid protein in cerebral tissues of diabetic rats / 第二军医大学学报

ABSTRACT

Objective: To analyze the association of recognition and behavior of diabetic rats with the expression of β-amyloid protein (Aβ) and cAMP response element binding protein (CREB), so as to pave a way for studying the role of diabetic metabolic disorder in the mechanism of Alzheimer's disease. Methods: Animal model of diabetes mellitus was established by intraperitoneal injection of streptozocin. Wistar rats were randomly divided into normal control groups (N), 4 week diabetes mellitus model group (M4), 6 week diabetes mellitus model group (M6), and 8 week diabetes mellitus model group(M8). The changes of recognition and behavior were tested by Morris water maze task and shuttle box task. Congo red staining was used to detect the deposition of beta-amyloid in the brain tissues. Expression of Aβ was measured by enzyme linked immunosorbent assay. CREB and pCREB were tested by enzyme linked immunosorbent assay, RT-PCR, and Western blotting assay. Results: Behavioral tests showed that the learning ability and memory of animals in the diabetes mellitus model groups were impaired and significantly decreased compared with those in the normal control group(P<0.01). Compared with the normal control group, the model groups showed higher Aβ expression and lower CREB and pCREB expression (P < 0.01), with no significant difference found between the three model groups. The expression of Aβ was negatively correlated with the expression of CREB and pCREB, and was positively correlated with learning and memory impairment of animals. CREB and pCREB were negatively correlated with the learning ability and memory impairment of animals. Conclusion: Diabetes mellitus can contribute to Alzheimer's disease through increasing expression of Aβ and decreasing expression of CREB and pCREB.