(Plos) - “Wine is the most healthful and most hygienic of beverages”, said Louis Pasteur. Through the biological activity of several classes of organic compounds such as anthocyanins, tannins and flavonoids, red wine is known to have beneficial effects on health, when consumed in moderation. These natural organic compounds, in particular flavonoids, show anti-inflammatory, anti-oxidant and anti-aging properties, thus beneficially affecting health. However, the cellular and molecular mechanisms underlying the positive effects of flavonoids remain unknown.

In a recent paper published in PLOS ONE, Torres-Perez and colleagues investigated the neurobiological effects of the natural flavonoid found in grapes Resveratrol (RVTL) on hippocampal neuroplasticity and cognitive performance in rodents using a wide range of techniques (Torres-Perez et al., 2015). Although several reports have already highlighted a neuroprotective effect of RVTL (Sonmez et al., 2007; Vingtdeux et al., 2010), its neuroprotective mechanisms have remained elusive. As such, Torres-Perez and coauthors decided to explore the complex beneficial effects of RVTL on the hippocampus, a key brain region involved in aging as well as in learning and memory functions.

Effect of Resveratrol on cell survival and proliferation.

Cell survival and proliferation of hippocampal neurons may counteract the cognitive decline usually observed during aging; therefore, the primary focus of the authors was on the potential effect of RVTL on these two mechanisms. To this end, hippocampi of 6-month old mice treated for 14 consecutive days with RVTL at different doses (1-40 mg/kg) were analyzed by immunohistochemistry paying particular attention to the dentate gyrus. Based on the expression of cellular markers specific for cell proliferation (Ki67), cell survival (BrdU) and early stage of neuronal development (Doublecortine, DCX), Torres-Perez and colleagues reported that Resveratrol is able to promote cell survival and neurogenesis in the mouse hippocampus.

These results indicate that RVTL has an important impact on neuronal plasticity, thus providing evidence of neuroprotective activity. According to the authors, “the survival of new born cells is of central importance, particularly because [their] general hypothesis is that adult hippocampal neurogenesis provides a «neurogenic reserve» that allows for the maintenance of cognitive flexibility in older age”. In spite of the relevance of this finding, the authors knew that cell survival itself might not be the only mechanism through which RVTL could act on the brain and so they explored other alternatives as well.

Effect of Resveratrol on neuronal morphology.

Neurons are complex elements exhibiting a sophisticated morphology characterized by small boutons (spines) on their dendrites. Dendritic spines assure the flow of information between neurons and among brain structures and are subject to continuous remodeling. It is thought that this structural remodeling is an essential mechanism for learning and memory functions since a reduction in dendritic spine number has been associated with cognitive decline (e.g. Alzheimer’s disease).

Consequently, Torres-Perez and coauthors decided to carefully scrutinize the morphology of dendritic spines in RVTL-treated mice. Interestingly, they observed that RVTL was able to increase both the number of dendritic spines and the proportion of mature dendritic boutons, which suggests that RVTL may have a“beneficial effect on the learning and memory processes”, according to Dr. Ramirez-Rodriguez, team leader and senior scientist of the study.