Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi

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 and Zhou, Xin-Wen (2013) Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi. Age, 36 2: 613-623. doi:10.1007/s11357-013-9592-1


Author 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
Title Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi
Journal name Age   Check publisher's open access policy
ISSN 0161-9152
1574-4647
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s11357-013-9592-1
Open Access Status DOI
Volume 36
Issue 2
Start page 613
End page 623
Total pages 11
Place of publication Dordrecht, The Netherlands
Publisher Springer Netherlands
Collection year 2014
Language eng
Subject 2717 Geriatrics and Gerontology
1302 Curriculum and Pedagogy
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.
Keyword Streptozotocin
Tau phosphorylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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