Neuroprotection of resveratrol against neurotoxicity induced by methamphetamine in mouse mesencephalic dopaminergic neurons

Biofactors. 2015 Jul-Aug;41(4):252-60. doi: 10.1002/biof.1221. Epub 2015 Jul 24.

Abstract

Resveratrol is originally extracted from huzhang, a Chinese herbal medicine. Recently, resveratrol has attracted a great of attention due to its antioxidant and antiapoptotic properties. Although the neuroprotection of resveratrol on neural damages in various models has been well characterized, little is known about the role of resveratrol in methamphetamine (MA) induced neurotoxicity in mesencephalic dopaminergic neurons. Dopaminergic neurons were isolated from midbrain of mouse embryos at embryonic day 15 and cultured in the presence of MA and resveratrol. Cell viability was examined by MTT assay and the apoptosis was assessed using Hoechst33342/PI double staining. To evaluate the Oxidative damage, ROS assay was performed. Moreover, the changes of time course of intracellular free calcium concentration ([Ca(2+) ]i) were analyzed with Fluo-3/AM tracing. The data showed that MA induced the neurotoxicity of cultured cells in a dose-dependent manner. Resveratrol significantly increased cellular viability and retarded cell apoptosis. Furthermore, resveratrol also attenuated MA induced ROS production and intracellular free calcium overload. Our results suggest that resveratrol protects dopaminergic neurons from MA-induced neuronal cytotoxicity, which, at least partly, is mediated by inhibition of [Ca(2+) ]i and oxidative stress. © 2015 BioFactors 41(4):252-260, 2015.

Keywords: calcium; methamphetamine; oxidative stress; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Calcium / metabolism
  • Cell Survival / drug effects
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / antagonists & inhibitors*
  • Dopamine Uptake Inhibitors / toxicity
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Embryo, Mammalian
  • Fluorescent Dyes
  • Mesencephalon / cytology
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Methamphetamine / antagonists & inhibitors*
  • Methamphetamine / toxicity
  • Mice
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress
  • Primary Cell Culture
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*
  • Xanthenes

Substances

  • Aniline Compounds
  • Antioxidants
  • Dopamine Uptake Inhibitors
  • Fluorescent Dyes
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Stilbenes
  • Xanthenes
  • Fluo-3
  • Methamphetamine
  • Resveratrol
  • Calcium
  • Dopamine