Hyperphosphorylation of Tau Protein in Hippocampus of Central Insulin-Resistant Rats is Associated with Cognitive Impairment

Cellular Physiology and Biochemistry

关键词: Insulin resistance;    Streptozotocin;    Hyperphosphorylation;    Tau protein;    Alzheimer';    s disease;   

DOI  :  10.1159/000356579

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Peripheral insulin resistance increases the risk for memory impairment and the development of AD. Objective This study aims to assess changes in cognitive functions and the level of hyperphosphorylated tau proteins in central insulin-resistant rats. Methods An in vivo central insulin-resistant (CIR) animal model was generated through intracerebroventricular injection of streptozotocin (STZ) into insulin-resistant (IR) rats that were induced by feeding a high-glucose/-protein/-fat diet. The Morris water maze test was used to assess changes in cognitive functions, pathological changes in the cornu ammonis 1 (CA1) region of the hippocampus were detected by immunohistochemistry, and the phosphorylation levels of tau proteins at specific sites were determined by Western blot analysis. Results The escape latency time in the Morris water maze test was significantly prolonged; the number of phosphorylated tau proteins in the CA1 region of the hippocampus was significantly increased; and the phosphorylation levels of tau proteins at Ser199, Thr205, Thr212, Thr217 and Ser396 were significantly elevated in the CIR group compared with the IR and control groups. Conclusion This study provides direct evidence that CIR plays an important role in AD pathogenesis by facilitating tau hyperphosphorylation.

【 授权许可】

CC BY-NC-ND