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Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi.
Age (Dordr). 2014 Apr; 36(2):613-23.A

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.

Authors+Show Affiliations

Department of Pathophysiology, Key Laboratory of Neurological Diseases of Education Ministry of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24142524

Citation

Du, Lai-Ling, et al. "Activation of Sirtuin 1 Attenuates Cerebral Ventricular Streptozotocin-induced Tau Hyperphosphorylation and Cognitive Injuries in Rat Hippocampi." Age (Dordrecht, Netherlands), vol. 36, no. 2, 2014, pp. 613-23.
Du LL, Xie JZ, Cheng XS, et al. Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi. Age (Dordr). 2014;36(2):613-23.
Du, L. L., Xie, J. Z., Cheng, X. S., Li, X. H., Kong, F. L., Jiang, X., Ma, Z. W., Wang, J. Z., Chen, C., & Zhou, X. W. (2014). Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi. Age (Dordrecht, Netherlands), 36(2), 613-23. https://doi.org/10.1007/s11357-013-9592-1
Du LL, et al. Activation of Sirtuin 1 Attenuates Cerebral Ventricular Streptozotocin-induced Tau Hyperphosphorylation and Cognitive Injuries in Rat Hippocampi. Age (Dordr). 2014;36(2):613-23. PubMed PMID: 24142524.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi. AU - Du,Lai-Ling, AU - Xie,Jia-Zhao, AU - Cheng,Xiang-Shu, AU - Li,Xiao-Hong, AU - Kong,Fan-Li, AU - Jiang,Xia, AU - Ma,Zhi-Wei, AU - Wang,Jian-Zhi, AU - Chen,Chen, AU - Zhou,Xin-Wen, Y1 - 2013/10/20/ PY - 2012/11/20/received PY - 2013/10/07/accepted PY - 2013/10/22/entrez PY - 2013/10/22/pubmed PY - 2014/11/19/medline SP - 613 EP - 23 JF - Age (Dordrecht, Netherlands) JO - Age (Dordr) VL - 36 IS - 2 N2 - 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. SN - 1574-4647 UR - https://www.unboundmedicine.com/medline/citation/24142524/Activation_of_sirtuin_1_attenuates_cerebral_ventricular_streptozotocin_induced_tau_hyperphosphorylation_and_cognitive_injuries_in_rat_hippocampi_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24142524/ DB - PRIME DP - Unbound Medicine ER -