Stimulation of SIRT1 Attenuates the Level of Oxidative Stress in the Brains of APP/PS1 Double Transgenic Mice and in Primary Neurons Exposed to Oligomers of the Amyloid-β Peptide

Article type: Research Article

Authors: Dong, Yang-Ting^{a; b} | Cao, Kun^{a; b} | Tan, Long-Chun^{b; c} | Wang, Xiao-Ling^{b; c} | Qi, Xiao-Lan^{b; c} | Xiao, Yan^{a; b} | Guan, Zhi-Zhong^{a; b; c; *}

Affiliations: [a] Department of Pathology at the Affiliated Hospital of Guizhou Medical University, Guiyang, P. R. China | [b] Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guizhou Medical University, Guiyang, P. R. China | [c] Key Laboratory of Medical Molecular Biology, Guiyang, P. R. China

Correspondence: [*] Correspondence to: Zhi-Zhong Guan, Department of Pathology at the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, P. R. China. E-mails: 1457658298@qq.com or zhizhongguan@yahoo.com.

Abstract: In the study, we examined whether the silent information regulator 1 (SIRT1) can attenuate oxidative stress in the brains of mice carrying the APP/PS1 double mutation and/or in primary neonatal rat neurons exposed to oligomers of amyloid-β peptide (AβOs). Starting at 4 or 8 months of age, the transgenic mice were treated with resveratrol (RSV, a stimulator of SIRT1) or suramin (an inhibitor) (each 20 mg/kg BW/day) for two months. The primary neurons were exposed to AβOs (0.5 μM) for 48 h and thereafter RSV (20 μM) or suramin (300 mg/ml) for 24 h. Cell viability was assessed by the CCK-8 assay; SIRT1 protein and mRNA determined by western blotting and real-time PCR, respectively; senile plaques examined immunohistochemically; ROS monitored by flow cytometry; and the contents of OH-, H2O2, O2·-, and MDA, and the activities of SOD and GSH-Px measured by standard biochemical procedures. In comparison to wild-type mice or untreated primary neurons, the expression of SIRT1 was significantly lower in the brains of APP/PS1 mice or neurons exposed to AβOs. In these same systems, increased numbers of senile plaques and a high level of oxidative stress were apparent. Interestingly, these two latter changes were attenuated by treatment with RSV, but enhanced by suramin. These findings indicate that SIRT1 may be neuroprotective.

Keywords: AβOs, APP/PS1 mice, oxidative stress, primary neurons, resveratrol, SIRT1, suramin

DOI: 10.3233/JAD-171020

Journal: Journal of Alzheimer's Disease, vol. 63, no. 1, pp. 283-301, 2018