title: 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.
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing Geriatric Medical Research Center, #45 Changchun Street, Xicheng District, Beijing, 100053, China.
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Meng
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhao
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Wang
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Ma
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Sheng
authors.forename: Zhi-Juan
authors.initials: ZJ
authors.lastname: Ji
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000503:physiopathology*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000633:toxicity; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C000602555:APP5-mer peptide; D016564:Amyloid beta-Protein Precursor; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013311:Streptozocin; D011972:Receptor, Insulin