Neuroprotective Effects of Resveratrol on MPTP-Induced Neuron Loss Mediated by Free Radical Scavenging

Abstract

Resveratrol is a natural polyphenol and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and myocardial infraction. Parkinson's disease is a common progressive neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the most useful neurotoxin to induce Parkinsonism. The present study was carried out to elucidate the neuroprotective effect and possible mechanism of resveratrol on MPTP-induced striatal neuron loss. Sixty adult Balb/c mice were divided into four groups: sham operation, MPTP treatment (30 mg/kg, i.p.), MPTP combined with resveratrol administration (20 mg/kg, i.v.), and resveratrol treatment alone. Microdialysis and high-performance liquid chromatography were used to analyze dihydroxybenzoic acid (DHBA) that reflected the hydroxyl radical level. In the present study, we found MPTP chronic administration significantly induced motor coordination impairment in mice. After MPTP administration, the hydroxyl radical levels in substantia nigra were also significantly elevated and animals displayed severe neuronal loss. Resveratrol administration significantly protected mice from MPTP-induced motor coordination impairment, hydroxyl radical overloading, and neuronal loss. Our results demonstrated that resveratrol could elicit neuroprotective effects on MPTP-induced Parkinsonism through free radical scavenging.

Nutrition, Brain Aging, and Neurodegeneration: Table 1.

“…Knock-out of sirt2 in invertebrates eliminated the lifespan extension induced by CR while overexpression increased lifespan similar to CR (Guarente, 2007;Michan and Sinclair, 2007;Lavu et al, 2008). Results from a variety of recent studies in rodent models show that resveratrol can produce a remarkable range of beneficial effects including protection against high fat diets, neurodegeneration and agerelated pathologies, such as cardiac function and cataracts Fukuda et al, 2006;Kim et al, 2007;Lu et al, 2008;Pearson et al, 2008), and motor declines (Pearson et al, 2008), but did not significantly increase lifespan in mice on a normal diet (Pearson et al, 2008).…”

Effect of Resveratrol Supplementation on the Performance of Dogs in an Eight-Arm Radial Maze

“…Resveratrol, a plant-derived phytoestrogen, may minimise the deterioration in cognitive function associated with physical and chemical damage to the brain [1][2][3][4][5][6][7]. In rats and mice, resveratrol has been found to minimise the adverse brain and cognitive changes induced by neurologically damaging events such as streptozotocin-induced diabetes [1]; percussive cerebral trauma [2]; focal cerebral ischemia (stroke) [3]; oxidative stress caused by intracerebroventricular injection of streptozotocin [4] or cochinine [5]; and neurotoxic substances used to mimic Huntington's disease [6] and Parkinson's disease [7].…”

“…In rats and mice, resveratrol has been found to minimise the adverse brain and cognitive changes induced by neurologically damaging events such as streptozotocin-induced diabetes [1]; percussive cerebral trauma [2]; focal cerebral ischemia (stroke) [3]; oxidative stress caused by intracerebroventricular injection of streptozotocin [4] or cochinine [5]; and neurotoxic substances used to mimic Huntington's disease [6] and Parkinson's disease [7]. Resveratrol has been shown to decrease lipid peroxidation and up-regulate antioxidant enzymes in the brains of healthy male rats [8].…”

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

“…Radical scavenging activity in mice has already been applied in several studies using an intraperitoneal (i.p.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Ferger et al, 1999;Lu et al, 2008;Thomas et al, 2000). Generally, the in vivo hydroxyl radical generation in the striatum of mice was analyzed by administrating salicylate i.p.…”

“…Generally, the in vivo hydroxyl radical generation in the striatum of mice was analyzed by administrating salicylate i.p. just before sacrificing the mice or performing microdialysis and determining in real-time the hydroxyl radical generation by striatal perfusion with salicylate (Ferger et al, 1999;Lu et al, 2008;Thomas et al, 2000). In another study, the systemic administration of 3,4-methylendioxymetamphetamine induced free radical formation in mouse striatum was studied with the in vivo salicylate trapping microdialysis (Camarero et al, 2002).…”