Neuroprotection by Tetrahydroxystilbene Glucoside in the MPTP Mouse Model of Parkinson's Disease

Toxicol Lett. 2013 Oct 24;222(2):155-63. doi: 10.1016/j.toxlet.2013.07.020. Epub 2013 Aug 1.

Abstract

Our in vitro experiments suggested that tetrahydroxystilbene glucoside (TSG) affords a significant neuroprotective effect against MPP⁺-induced damage and apoptosis in PC12 cells though activation of the PI3K/Akt pathway. This study was aimed to investigate the potential neuroprotective effect of TSG in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-treated mouse model of Parkinson's disease (PD). We found that treatment of TSG protected dopaminergic neurons by preventing MPTP-induced decreases in substantia nigra tyrosine hydroxylase (TH)-positive cells and striatal dopaminergic transporter (DAT) protein levels. Furthermore, it was also associated with increasing striatal Akt and GSK3β phosphorylation, up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that TSG promoted dopamine neuron survival in vivo, the PI3K/Akt signaling pathway may have mediated the protection of TSG against MPTP, suggesting that TSG treatment might represent a neuroprotective treatment for PD.

Keywords: Neuroprotection; Parkinson's disease; Phosphatidylinositol 3-kinase (PI3K)/Akt; Tetrahydroxystilbene glucoside; Tyrosine hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Ataxia / etiology
  • Ataxia / prevention & control
  • Behavior, Animal / drug effects
  • Cell Survival / drug effects
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Disease Models, Animal*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Glucosides / therapeutic use*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / physiopathology
  • Parkinson Disease / prevention & control*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Stilbenes / therapeutic use*
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Glucosides
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Slc6a3 protein, mouse
  • Stilbenes
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Akt1 protein, mouse
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3