En Xin-Wen ZhouReceived: 20 November 2012 / Accepted: 7 October 2013 / Published

En Xin-Wen ZhouReceived: 20 November 2012 / Accepted: 7 October 2013 / Published on the web: 20 October 2013 # American Aging AssociationAbstract Sufferers with diabetes inside the aging population are at higher risk of Alzheimer’s disease (AD), and reduction of sirtuin 1 (SIRT1) activity occurs simultaneously together with the accumulation of hyperphosphorylated tau within the AD-affected brain. It truly is not clear, having said that, no matter whether SIRT1 can be a appropriate molecular target for the treatment of AD. Here, we employed a rat model of brain insulin resistance with Caspase 9 Inhibitor supplier intracerebroventricular injection of streptozotocin (ICV-STZ; three mg/kg, twice with an interval of 48 h). The ICV-STZ-treated rats had been administrated with resveratrol (RSV; SIRT1-specific activator) or perhaps a automobile via intraperitoneal injection for 8 weeks (30 mg/kg, when each day). In ICV-STZ-treated rats, the levels of phosphorylated tau and phosphorylated extracellular signal-regulated kinases 1 and two (ERK1/2) at the hippocampi had been enhanced considerably, whereas SIRT1 activity was decreased devoid of modify of its expression level. The capacity of spatial memory was also drastically decrease in ICV-STZ-treated rats compared with age-matched control. RSV, a distinct 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. Keywords SIRT1 . Tau phosphorylation . ERK1/2 . StreptozotocinIntroduction Various epidemiological studies have shown that sort two diabetes mellitus (T2DM) increases the risk of Alzheimer’s disease (AD) (Arvanitakis et al. 2004; Stewart and Liolitsa 1999; Sanz et al. 2012). T2DM shares numerous widespread characteristics with AD, such as disrupted glucose metabolism, insulin resistance, and cognitive impairment (Arvanitakis et al. 2004; Liu et al. 2011). It is thus suggested that there is a convergent point among these two diseases. Proof exists to help that defective brain insulin signaling contributes to the occurrence of AD (Hoyer and Nitsch 1989). Streptozotocin (STZ) has been accepted broadly as a drug to induce animal models of both DM and AD. Earlier research have shown thatLai-Ling Du and Jia-Zhao Xie contributed equally to this operate L.L. Du : J.Z. Xie : X.S. Cheng : X.H. Li : F.L. Kong : X. Jiang : Z.W. Ma : J.Z. Wang : X.W. Zhou () Department of Pathophysiology, Crucial Laboratory of Neurological Illnesses of Education Ministry of China, Tongji Health-related D4 Receptor Agonist site College, Huazhong University of Science and Technologies, Wuhan 430030, China e-mail: [email protected] C. Chen School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, AustraliaAGE (2014) 36:613?intracerebroventricular (ICV) injection of STZ induces brain insulin resistance by way of the reduction of insulin receptor (IR) expression and causes desensitization of IRs (Plaschke et al. 2010). ICV-STZ therapy causes impairment of brain glucose metabolism top to oxidative anxiety, which facilitates the alternation of AD-like pathology, including production of -amyloid (A) and tau hyperphosphorylation and cognitive impairment. The model of ICV-STZ has been thought of as a valid experimental model to discover etiology of sporadic Alzheimer’s disease (sAD) (Grunblatt et al. 2007; Hoyer and Lanner.