ABSTRACT
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.
Subject(s)
Cognitive Dysfunction/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Glucagon-Like Peptide 1/pharmacology , Animals , Blood Glucose/metabolism , Cognitive Dysfunction/blood , Cognitive Dysfunction/metabolism , Cytoskeletal Proteins/metabolism , Diabetes Mellitus, Type 2/blood , Diet, High-Fat/adverse effects , Disease Models, Animal , Hippocampus/drug effects , Male , Maze Learning/drug effects , Memory Disorders/complications , Nerve Tissue Proteins/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To investigate the effect of glucagon-like peptide 1 (GLP-1) on cognitive dysfunction in diabetic rats. METHODS: Male SD rats were randomly divided into normal control group, diabetes mellitus (DM) group, and GLP-1 treatment group. Rat models of type 2 diabetes were established by high-sugar and high-fat feeding and streptozotocin (STZ) injection, and 25 days after the onset of diabetes, GLP-1 was infused in GLP-1 treatment group at the rate of 30 pmol·kg-1·min-1 via a subcutaneous osmotic pump for 7 days. The learning and cognitive ability of the rats was assessed with Morris water maze test, and the expression of cognition-related genes in the hippocampus tissue was detected with real-time PCR, Western blotting and immunohistochemical staining. RESULTS: Compared with the normal control group, the diabetic rats showed significantly decreased learning and memory abilities (P<0.05) with increased hippocampal expressions of APP, BACE1, Arc, ERK1/2, PKA, and PKC mRNAs (P<0.05) and Arc protein. Compared with diabetic rats, GLP-1-treated rats showed significantly improvements in the learning and memory function (P<0.05) with decreased expressions of APP, BACE1, Arc, ERK1/2, and PKA mRNAs (P<0.05) and Arc protein. CONCLUSION: GLP-1 can improve cognitive dysfunctions in diabetic rats possibly by regulating the PKC, PKA, and ERK1/2 pathways and inhibiting Arc expression in the hippocampus.
