Red wine antioxidants protect hippocampal neurons against ethanol-induced damage: a biochemical, morphological and behavioral study.

Chronic ethanol consumption increases oxidative stress, which accounts for the striking neurological changes seen in this condition. Notwithstanding, there is well-documented evidence that polyphenols, present in grape skin and seeds, exhibit a strong antioxidant activity. As red wine is rich in polyphenols, the aim of the present work was to evaluate their putative protective effects on the hippocampal formation by applying biochemical, morphological and behavioral approaches. Six-month old male Wistar rats were fed with red wine (ethanol content adjusted to 20%) and the results were compared with those from ethanol-treated (20%) rats and pair-fed controls. Biochemical markers of oxidative stress (lipid peroxidation, glutathione levels and antioxidant enzyme activities) were assessed on hippocampal homogenates. Lipofuscin pigment, an end product of lipid peroxidation, was quantified in hippocampal cornu ammonis 1 and 3 (CA1 and CA3) pyramidal neurons using stereological methods. All animals were behaviorally tested on the Morris water maze in order to assess their spatial learning and memory skills. In red wine-treated rats, lipid peroxidation was the lowest while presenting the highest levels of reduced glutathione and an induction of antioxidant enzyme activities. Morphological findings revealed that, contrary to ethanol, red wine did not increase lipofuscin deposition in CA1 and CA3 pyramidal neurons. Besides, red wine-treated animals learned the water maze task at a higher rate than ethanol group and had better performance scores by the end of the training period and on a probe trial. Actually, no significant differences were found between pair-fed controls and red wine-treated rats in morphological and behavioral data. Thus, our findings demonstrate that chronic consumption of red wine, unlike the ethanol solution alone, does not lead to a decline in hippocampal-dependent spatial memory. This may be due to the ability of red wine polyphenols to improve the antioxidant status in the brain and to prevent free radical-induced neuronal damage.