Biochem Pharmacol. 2007 Feb 15;73(4):550-60. Epub 2006 Nov 9.

Resveratrol protects dopaminergic neurons in midbrain slice culture
from multiple insults.


Okawara M, Katsuki H, Kurimoto E, Shibata H, Kume T, Akaike A.


Department of Pharmacology, Graduate School of Pharmaceutical
Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku,
Kyoto 606-8501, Japan.


Increasing lines of evidence show that resveratrol, a polyphenol
compound contained in several dietary products, exhibits
cytoprotective actions. Notably, resveratrol activates sirtuin family
of NAD-dependent histone deacetylases implicated in regulation of
various cellular processes including gene transcription, DNA repair
and apoptosis. Here we examined neuroprotective effect of resveratrol
on dopaminergic neurons in organotypic midbrain slice culture.
Resveratrol and quercetin, another sirtuin-activating polyphenol,
prevented the decrease of dopaminergic neurons and the increase of
propidium iodide uptake into slices induced by a dopaminergic
neurotoxin 1-methyl-4-phenyl pyridinium (MPP(+)). Resveratrol also
provided concentration-dependent neuroprotective effects against
sodium azide, a mitochondrial complex IV inhibitor, and thrombin (EC
number 3.4.21.5), a microglia-activating agent. Sirtuin inhibitors
such as nicotinamide and sirtinol did not attenuate the protective
effect of resveratrol against MPP(+) cytotoxicity. Instead, we found
that resveratrol prevented accumulation of reactive oxygen species,
depletion of cellular glutathione, and cellular oxidative damage
induced by MPP(+), suggesting involvement of antioxidative properties
in the neuroprotective action of resveratrol. On the other hand,
resveratrol as well as a sirtuin activator NAD inhibited dopaminergic
neurotoxicity of a DNA alkylating agent, N-methyl-N'-nitro-N-
nitrosoguanidine (MNNG). Moreover, MNNG-induced increase in
acetylation of p53, a representative target of sirtuin deacetylase
activity, was suppressed by resveratrol. These results indicate that
resveratrol can exert neuroprotective actions in dopaminergic neurons.
Either antioxidative activity or sirtuin-activating potential may play
an important role in the neuroprotectice actions of resveratrol
against different kinds of insults.


PMID: 17147953 [PubMed - indexed for MEDLINE]