N Xin-Wen ZhouReceived: 20 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 online: 20 October 2013 # American Aging AssociationAbstract Sufferers with diabetes within the aging population are at higher danger of Alzheimer’s illness (AD), and reduction of sirtuin 1 (SIRT1) activity happens simultaneously together with the accumulation of hyperphosphorylated tau inside the AD-affected brain. It is not clear, having said that, regardless of whether SIRT1 can be a suitable molecular target for the treatment 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 were administrated with resveratrol (RSV; SIRT1-specific activator) or maybe a automobile via intraperitoneal injection for 8 weeks (30 mg/kg, after per day). In ICV-STZ-treated rats, the levels of phosphorylated tau and phosphorylated extracellular BACE1 Purity & Documentation signal-regulated kinases 1 and two (ERK1/2) in the hippocampi were elevated considerably, whereas SIRT1 activity was decreased without adjust of its expression level. The capacity of spatial memory was also drastically reduced in ICV-STZ-treated rats compared with age-matched handle. RSV, a particular activator of SIRT1, which reversed the ICV-STZ-induced lower 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 type 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 several typical characteristics with AD, which include disrupted glucose metabolism, insulin resistance, and cognitive impairment (Arvanitakis et al. 2004; Liu et al. 2011). It is for that reason suggested that there is a convergent point involving these two ailments. Evidence exists to assistance that defective brain insulin signaling contributes to the occurrence of AD (Hoyer and Nitsch 1989). Streptozotocin (STZ) has been accepted extensively as a drug to induce animal models of each DM and AD. Earlier 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, Important 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 College of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, AustraliaAGE (2014) 36:613intracerebroventricular (ICV) injection of STZ induces brain insulin resistance through 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 major to oxidative strain, which facilitates the alternation of AD-like pathology, including production of –Caspase 6 Storage & Stability amyloid (A) and tau hyperphosphorylation and cognitive impairment. The model of ICV-STZ has been regarded as as a valid experimental model to explore etiology of sporadic Alzheimer’s disease (sAD) (Grunblatt et al. 2007; Hoyer and Lannert.