Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi
| Autor: | Jian-Zhi Wang, Xiang-Shu Cheng, Xin-Wen Zhou, Xiao-Hong Li, Fan-Li Kong, Lai-Ling Du, Chen Chen, Zhi-Wei Ma, Xia Jiang, Jia-Zhao Xie |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Aging medicine.medical_specialty endocrine system diseases MAP Kinase Signaling System Vasodilator Agents medicine.medical_treatment Blotting Western Intraperitoneal injection tau Proteins Resveratrol Hippocampus Antioxidants Streptozocin Article Cerebral Ventricles Rats Sprague-Dawley chemistry.chemical_compound Cognition Insulin resistance Sirtuin 1 Internal medicine Stilbenes medicine Animals Hippocampus (mythology) Fluorometry Phosphorylation biology Kinase Activator (genetics) General Medicine Streptozotocin medicine.disease Rats Disease Models Animal enzymes and coenzymes (carbohydrates) Endocrinology chemistry biology.protein Rabbits Geriatrics and Gerontology Cognition Disorders Injections Intraperitoneal hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | AGE. 36:613-623 |
| ISSN: | 1574-4647 0161-9152 |
| DOI: | 10.1007/s11357-013-9592-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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