Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease

Restor Neurol Neurosci. 2013;31(1):41-52. doi: 10.3233/RNN-120260.

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(-1)d(-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / genetics*
  • Animals
  • Blotting, Western
  • Brain Chemistry / drug effects
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Data Interpretation, Statistical
  • Glucosides / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microarray Analysis
  • Nootropic Agents / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Stilbenes / pharmacology*
  • alpha-Synuclein / biosynthesis*

Substances

  • Amyloid beta-Protein Precursor
  • DNA, Complementary
  • Glucosides
  • Nootropic Agents
  • RNA, Messenger
  • Stilbenes
  • alpha-Synuclein
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside