1. Effects of analog P165 of amyloid precursor protein 5-mer peptide on learning, memory and brain insulin receptors in the rat model of cognitive decline.
- Author
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Xu BL, Wang R, Meng XH, Zhao ZW, Wang HJ, Ma LN, Dong W, Sheng SL, and Ji ZJ
- Subjects
- Animals, Brain metabolism, Disease Models, Animal, Hypoglycemic Agents pharmacology, Insulin metabolism, Male, Rats, Rats, Sprague-Dawley, Rosiglitazone, Signal Transduction drug effects, Streptozocin toxicity, Thiazolidinediones pharmacology, Amyloid beta-Protein Precursor pharmacology, Brain drug effects, Cognition Disorders physiopathology, Maze Learning drug effects, Memory drug effects, Peptide Fragments pharmacology, Receptor, Insulin metabolism
- Abstract
We aim to study the therapeutic efficacy of analog P165 of amyloid precursor protein 5-mer peptide in streptozotocin (STZ)-induced cognitive decline model. Rats were divided into four groups: control, STZ, STZ+P165, and STZ+rosiglitazone (RSG). STZ model was established by intracerebroventricular injection of STZ. Three weeks following surgery, rats received daily gavage administration of distilled water (control and STZ groups), P165 (STZ+P165), or RSG (STZ+RSG) for four consecutive weeks. Learning and memory abilities were assessed with the Morris water maze test. Insulin-like growth factor-1 (IGF-1) was detected by ELISA. Expressions of insulin receptor-β (IR-β), insulin receptor substrate-1 (IRS-1), serine/threonine kinase (Akt), and phosphorylation of CREB (p-CREB) were observed by immunohistochemistry. Both P165 and RSG significantly reduced the escape latency relative to the STZ group (P165, P < 0.05; RSG, P < 0.01). STZ model rats had reduced levels of IGF-1 relative to control, and this deficit was attenuated in the STZ+P165 group (P < 0.01). IR and IRS-1 were elevated in STZ rats, and these levels were restored to near control in the STZ+P165 and STZ+RSG groups (P < 0.01). Our findings demonstrate that P165 and RSG improved hippocampus-dependent spatial learning and memory in STZ rats by regulating the insulin signaling pathway.
- Published
- 2014
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