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Could red wine improve cognitive performance?

“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.

Resveratrol increases the number of immature neurons in the 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.

Resveratrol induces spinogenesis.

Effect of Resveratrol on memory performance.

Whether cell survival and spine formation occurred in parallel with the potential neuroprotective effects of RVTL on associative memory remained unknown. To answer to this critical question, Torres-Perez and colleagues used the step-down passive avoidance (SDPA) method, which is sensitive to associative memory function. The SDPA test is a fear-aggravated model that involves learning to inhibit a response (natural exploratory drive) in order to avoid an aversive stimulus (footshock). The latency to repeat the punished response is considered to be an index of retention memory. Mice treated for 14 days with RVTL showed increased retention latency at both 1.5 hours (short-term) and 24 hours (long-term) after basal test, thus revealing improved cognitive performance. Such amelioration is thought to be specific to associative memories since working and reference memories, evaluated using the 8-radial arm maze test (8-RAM) behavioral paradigm, were not altered. “This finding provides additional evidence to support the hypothesis that RVTL exerts beneficial effects on the brain”, said the authors.

Resveratrol improves retention of associative memory in the passive avoidance behavioral test

Finally, at the cellular and molecular levels, cell survival, spine remodeling and memory formation require the activity of specific cell signaling players such as kinases. Among a plethora of signaling molecules, increased activities of two critical kinases, Akt and PKC, have been reported to correlate with neuroprotective events, as well as to shape neuronal cytoarchitecture. Hence, the authors of the study measured the levels of these two kinases in the hippocampus of RVTL-treated mice. Protein analysis revealed increased levels of activated Akt and PKC following treatment with RVTL, thus indicating that Akt- and PKC-dependent signaling pathways may be involved in the neuroprotective effects triggered by RVTL treatment.


Despite the richness of the findings presented by the authors, a direct and causal link between the observed phenomena and the neuroprotective properties of RVTL is still missing. For example, would inhibition of spine maturation be able to reverse RVTL-induced amelioration of memory performance? Would selective inhibition of Akt and PKC signaling pathways be capable of counteracting the beneficial effects of flavonoid treatment?

Future investigations are required to fully establish a complete and detailed picture of the mechanisms underlying the positive effects of this grape-derived natural compound on brain function. However, one thing is for certain: in a society characterized by an unbalanced life style, stress and fast-food alimentation, a healthy diet is a good move to help improve our brain function. What better place to start than wine — in moderation?


1. Torres-Pérez M, Tellez-Ballesteros RI, Ortiz-López L et al., (2015). Resveratrol Enhances Neuroplastic Changes, Including Hippocampal Neurogenesis, and Memory in Balb/C Mice at Six Months of Age. PLOS One 22;10(12):e0145687. doi: 10.1371/journal.pone.0145687. eCollection 2015.

2. Sonmez U, Sonmez A, Erbil G, Tekmen I, Baykara B (2007). Neuroprotective effects of resveratrol against traumatic brain injury in immature rats. Neurosci Lett. 2007;420(2):133–7. E

3. Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon JE, et al., (2010). AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem. 2010;285(12):9100–13


The author is grateful to Teresita Cruz for assistance.

Any views expressed are those of the author, and do not necessarily reflect those of PLOS. This article is not meant to encourage excessive alcohol consumption.   

Peppe-BWGiuseppe Gangarossa received his PhD in Biomedical Sciences, specialty Neuroscience, from the University of Bologna. He has been a visiting fellow at the Karolinska Institutet (Sotckholm, Sweden) and Inserm (Montpellier, France) and he is currently a postdoc at the Collège de France (Paris, France). His main research topic is dopamine-related brain disorders. You can follow him on twitter @PeppeGanga


  1. “Because resveratrol isn’t an essential nutrient, no required amount exists. Animal studies suggest as much as 500 mg daily may be necessary to provide any health benefits. Red wine contains at most 12.59 mg resveratrol per liter, so to get 500 mg daily, you’d need to drink almost 40 liters of wine daily. A 40 mg daily dose of resveratrol may also have some benefits, showed a study published in the “Journal of Clinical Endocrinology and Metabolism” in June 2010. Even if a 40 mg daily dose is sufficient, you’d still need to drink a little over 3 liters of wine daily to get that much resveratrol.”
    Showing a glass is a big lie.
    In the study commented as far as I remember they used 40 mg/kg for mice.
    So their is an effect of resveratrol but the required dose is unattainable in a standard diet.
    Can you comment on this issue?
    GA Pelouze MD

  2. Dear Dr. Pelouze,
    thanks a lot for your comment which is extremely interesting and scientifically correct. I agree with you, obviously it is not possible to drink 40 liters/day or even 3 liters/day of red wine. Excessive alcohol consumption is extremely dangerous.
    As you may know resveratrol is not found only in red wine but principally in grapes, chocolate, berries, nuts etc etc. A diet rich in flavonoids (several compounds belong to this family) has beneficial effects on health and a combination of several antioxidant molecules, more than a single compound, is likely to be the most appropriate approach to improve our health.
    The research article discussed in this blog post refers to a basic research study where only one variable is analyzed (effect of resveratrol vs control). Indeed this piece of pre-clinical research cannot be directly translated into clinical practice and it cannot be generalized to humans. This article attempts to dissect the cellular and molecular mechanisms of resveratrol-induced neuroprotective effects. More investigations are needed to fully explore the impact of flavonoids on our health.
    Giuseppe Gangarossa

  3. All I know is I drank a glass of wine for Christmas and I was suddenly answering quiz questions with more ease that I ever had done before! Maybe a little resveratrol is all we need. On a side note I usually don’t drink at all only once a year for Christmas and New Year,

    Also, my mother of 50 had a small sip and her eyesight noticeably improved.

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