Role of GSK3<i>β</i>and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

• 作者: Alfredo Meneses Enrique Hong Manuel Abascal-Díaz Teresa Ponce-Lopez
• 来源期刊: 阿尔茨海默氏病研究进展(英文)
• 学科: 医学
• 关键词: Memory Deficit Tau HYPERPHOSPHORYLATION GSK3β PP2A Streptozotocin HIPPOCAMPUS
• 年，卷（期）: 2017,（1）
• 页码范围: 13-31
• 页数: 19页
• 分类号: R73

摘要

Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer’s disease (AD) or older brains, so it has been proposed as a suitable model for studying some of the pathological features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A) in the regulation of the phosphorylation of tau (p-tau). Results showed that ICV-STZ treated rats had deficits in short- (1.5-h) and long-term (24- and 48-h) memory after one month of ICV-STZ treatment and six months relative to control rats. The memory deficit was associated to increasing [F(3, 12) = 31.48, p β (p-GSK3β) and PP2A in hippocampus and PFC, indicating that GSK3β and PP2A contributed to regulation of p-tau. These data supporting the model with ICV-STZ in rat are adequate to study the progressive memory impairment associated to hyperphosphorylation of tau and the cascade of insulin receptor signaling;confirm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt-GSK3β) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD.