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- Title
Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi.
- Authors
Du, Lai-Ling; Xie, Jia-Zhao; Cheng, Xiang-Shu; Li, Xiao-Hong; Kong, Fan-Li; Jiang, Xia; Ma, Zhi-Wei; Wang, Jian-Zhi; Chen, Chen; Zhou, Xin-Wen
- Abstract
Patients with diabetes in the aging population are at high risk of Alzheimer's disease (AD), and reduction of sirtuin 1 (SIRT1) activity occurs simultaneously with the accumulation of hyperphosphorylated tau in the AD-affected brain. It is not clear, however, whether SIRT1 is a suitable molecular target for the treatment of AD. Here, we employed a rat model of brain insulin resistance with intracerebroventricular injection of streptozotocin (ICV-STZ; 3 mg/kg, twice with an interval of 48 h). The ICV-STZ-treated rats were administrated with resveratrol (RSV; SIRT1-specific activator) or a vehicle via intraperitoneal injection for 8 weeks (30 mg/kg, once per day). In ICV-STZ-treated rats, the levels of phosphorylated tau and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) at the hippocampi were increased significantly, whereas SIRT1 activity was decreased without change of its expression level. The capacity of spatial memory was also significantly lower in ICV-STZ-treated rats compared with age-matched control. RSV, a specific activator of SIRT1, which reversed the ICV-STZ-induced decrease in SIRT1 activity, increases in ERK1/2 phosphorylation, tau phosphorylation, and impairment of cognitive capability in rats. In conclusion, SIRT1 protects hippocampus neurons from tau hyperphosphorylation and prevents cognitive impairment induced by ICV-STZ brain insulin resistance with decreased hippocampus ERK1/2 activity.
- Subjects
PHOSPHORYLATION; TAU proteins; SIRTUINS; STREPTOZOTOCIN; HIPPOCAMPUS (Brain); ALZHEIMER'S disease
- Publication
Age, 2014, Vol 36, Issue 2, p613
- ISSN
0161-9152
- Publication type
Article
- DOI
10.1007/s11357-013-9592-1