N Xin-Wen ZhouReceived: 20 CB2 web November 2012 / Accepted: 7 October 2013 / Published on line: 20 October 2013 # American Aging
N Xin-Wen ZhouReceived: 20 November 2012 / Accepted: 7 October 2013 / Published on the internet: 20 October 2013 # American Aging AssociationAbstract Patients with diabetes in the aging population are at higher threat of Alzheimer’s illness (AD), and reduction of sirtuin 1 (SIRT1) activity happens simultaneously together with the accumulation of hyperphosphorylated tau within the AD-affected brain. It really is not clear, even so, whether or not SIRT1 is actually a suitable molecular target for the remedy of AD. Right here, we employed a rat model of brain insulin resistance with intracerebroventricular injection of streptozotocin (ICV-STZ; three mg/kg, twice with an interval of 48 h). The ICV-STZ-treated rats have been administrated with resveratrol (RSV; SIRT1-specific activator) or a car by way of intraperitoneal injection for 8 weeks (30 mg/kg, when every day). In ICV-STZ-treated rats, the levels of phosphorylated tau and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the hippocampi have been increased significantly, whereas SIRT1 activity was decreased with no transform of its expression level. The capacity of spatial memory was also substantially reduce in ICV-STZ-treated rats compared with age-matched handle. RSV, a particular 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 phrases SIRT1 . Tau phosphorylation . ERK1/2 . StreptozotocinIntroduction Several epidemiological research have shown that sort two diabetes mellitus (T2DM) increases the risk of Alzheimer’s illness (AD) (Arvanitakis et al. 2004; Stewart and Liolitsa 1999; Sanz et al. 2012). T2DM shares lots of prevalent features with AD, such as disrupted glucose metabolism, insulin resistance, and cognitive impairment (Arvanitakis et al. 2004; Liu et al. 2011). It really is hence suggested that there is a convergent point between these two illnesses. Proof exists to help that defective brain insulin signaling contributes towards the occurrence of AD (Hoyer and Nitsch 1989). Streptozotocin (STZ) has been accepted widely as a drug to induce animal models of both DM and AD. Preceding research have shown thatLai-Ling Du and Jia-Zhao Xie contributed equally to this work 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, Essential Laboratory of Neurological Diseases of Education Ministry of China, Tongji Healthcare 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) 36:613intracerebroventricular (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 treatment causes impairment of brain glucose metabolism leading to oxidative stress, 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 regarded as a valid experimental model to discover etiology of MAO-B custom synthesis sporadic Alzheimer’s illness (sAD) (Grunblatt et al. 2007; Hoyer and Lannert.