title: Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model.
abstract: Brain metabolic dysregulation is a hallmark pathological change in Alzheimer's disease (AD). Although detailed mechanisms are still not fully elucidated, recent studies suggest alterations of insulin-signaling transduction cascades underlie neuronal stresses in AD brains. In this study, we performed in vivo experiments to determine the impact of soluble Aβ oligomers on insulin-signaling transduction in rat hippocampi by utilizing lateral ventricular injection of amyloid beta (Aβ) oligomers on male Wistar rats (225 ± 25 g, 3-4 months old) as an AD rat model. The Aβ-infused rats manifested remarkably increased escape latency and significantly decreased proportions of time and pathway crossing the hidden platform as compared to the rats in the pseudo-injection group and the non-injection group in Morris water maze test implicating the damaging effect of soluble Aβ oligomers on rat learning and memory functions. Accordingly, our subsequent results demonstrated that the infusion of soluble Aβ oligomers significantly decreased the expressions of insulin receptor, insulin receptor substrate-I, B cell lymphoma/leukemia-2 and serine/threonine protein kinase B in rat hippocampal neurons, whereas the expression level of total cAMP response element-binding protein was not changed. This study suggests that soluble Aβ oligomers instigated insulin-signaling disturbances which are potentially associated with learning and memory deficits in the AD rat model.
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324# Jingwu Weiqi Road, Jinan 250021, People's Republic of China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Shen
authors.initials: S
authors.lastname: Qi
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007859:Learning Disabilities / Q000209:etiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology*; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D050882:CREB-Binding Protein; D011972:Receptor, Insulin; D051058:Oncogene Protein v-akt