Glucagon-Like Peptide-1 (GLP-1) Treatment Ameliorates Cognitive Impairment by Attenuating Arc Expression in Type 2 Diabetic Rats

• Published in: Medical science monitor 2017-09, Vol.23, p.4334-4342
• Main Authors: Cai, Xiang-Sheng, Tan, Zhao-Guang, Li, Jing-Jing, Gao, Wei-Hong, Li, Shu-Ji, Li, Jin-Long, Tang, Yong-Ming, Li, Hong-Wei, Hui, Hong-Xiang
• Format: Article
• Language: English
• Subjects: Animal Study; Animals; Blood Glucose - metabolism; Cognitive Dysfunction - blood; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - metabolism; Cytoskeletal Proteins - metabolism; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diet, High-Fat - adverse effects; Disease Models, Animal; Glucagon-Like Peptide 1 - pharmacology; Hippocampus - drug effects; Male; Maze Learning - drug effects; Memory Disorders - complications; Nerve Tissue Proteins - metabolism; Rats; Rats, Sprague-Dawley
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.903252

BACKGROUND Glucagon-like peptide-1 (GLP-1) has been reported to exert some beneficial effects on the central nervous system (CNS). However, the effect of GLP-1 on cognitive impairment associated with type 2 diabetes is not well known. This study investigated the effect of GLP-1 on ameliorating memory deficits in type 2 diabetic rats. MATERIAL AND METHODS Type 2 diabetic rats were induced by a high-sugar, high-fat diet, followed by streptozotocin (STZ) injection and then tested in the Morris Water Maze (MWM) 1 week after the induction of diabetes. The mRNA expression of Arc, APP, BACE1, and PS1 were determined by real-time quantitative PCR, and the Arc protein was analyzed by immunoblotting and immunohistochemistry. RESULTS Type 2 diabetic rats exhibited a significant decline in learning and memory in the MWM tests, but GLP-1 treatment was able to protect this decline and significantly improved learning ability and memory. The mRNA expression assays showed that GLP-1 treatment markedly reduced Arc, APP, BACE1, and PS1 expressions, which were elevated in the diabetic rats. Immunoblotting and immunohistochemistry results also confirmed that Arc protein increased in the hippocampus of diabetic rats, but was reduced after GLP-1 treatment. CONCLUSIONS Our findings suggest that GLP-1 treatment improves learning and memory deficits in type 2 diabetic rats, and this effect is likely through the reduction of Arc expression in the hippocampus.