Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease
Affiliations: Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing, China | Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China
Note: [] Corresponding author: Lin Li, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Tel.: +86 10 83198886; Fax: +86 10 63042809; E-mails: [email protected] (L. Zhang); [email protected] (L. Li).
Note: [] Corresponding author: Lin Li, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Tel.: +86 10 83198886; Fax: +86 10 63042809; E-mails: [email protected] (L. Zhang); [email protected] (L. Li).
Abstract: Purpose: To investigate the mRNA and protein alterations of α-synuclein in the brain of Alzheimer's disease-like mouse model at the different ages, and to evaluate the effects of 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) on α-synuclein expression. Methods: TSG (120 or 240 μmol kg−1d−1) was intragastrically administered to APPV717I transgenic (Tg) mice at 4- or 10-month-old for 6 months. Results: mRNA expression of α-synuclein increased in hippocampus in 4 month to 16 month old Tg mice compared with age-matched control. α-synuclein protein expression in hippocampus also increased in 4 month to 16 month old Tg mice significantly. Significant down-regulation of α-synuclein mRNA and protein expression in hippocampus was found after treatment of TSG for 6 months in both 10- and 16-month-old Tg mice. Production of dimer and tetramer of α-synuclein protein in Tg mice was inhibited after treatment with TSG. Conclusions: The expression and aggregation of α-synuclein was age-dependently increased in Tg mice. TSG not only prevents over-expression of α-synuclein at an early stage, but also reverses the increased expression of α-synuclein and inhibits the aggregation at the late stage of Tg mice. TSG may have potential to the prevention and treatment of Alzheimer's diseases.
