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.

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.