Resveratrol Rejuvenates Rodent Recognition Memory: The Plant-Based Antioxidant Improves Cognition and Brain Blood Flow in Aging Rats

There is an increasing prevalence of coincident deficiency of the blood vessel (vascular) network in the brain and cognitive dysfunction with aging. At the root of this impairment to cerebral vascularization appears to be increased oxidative stress and inflammation that occur with aging.

Interestingly, the plant-derived compound resveratrol is known to be a strong, natural antioxidant that possesses anti-inflammatory properties. This has led researchers to speculate that resveratrol could protect against cerebral vascularization defects and improve the decline of cognitive function associated with aging.

Now, researchers from Aix-Marseille University have shown that long-term treatment with low-dose resveratrol improves cognitive performance in the elderly male rat model. Their research, published in the Journal for Nutritional Biochemistry, found that this effect is associated with an increase in cerebral blood flow and a decrease in the expression of several pro-inflammatory pathways in the brain. 

Blood flow and brain health

Normal aging is associated with modifications to the mechanical properties of blood vessels. These modifications are involved in anatomical and functional alterations in the brain vasculatures that lead to poor blood flow and potentially neurodegeneration. Also, there is an increasing prevalence of coincident cerebrovascular deficiency and cognitive dysfunction with aging that is also well recognized in Alzheimer’s disease.

Resveratrol’s restorative reaches

Resveratrol is a natural phytoalexin — a substance that is produced by plant tissues in response to contact with a parasite and specifically inhibits the growth of that parasite — produced by various plants like the red grapes, peanuts, and berries. The beneficial properties of trans-resveratrol are extensively depicted in the literature and include anti-inflammatory, antioxidant, analgesic, and anti-tumoral activities.

Protective effects against cardiovascular and neurodegenerative diseases as well as metabolic effects on bone and glucose metabolism have also been described. Evidence in research animals supports the notion that resveratrol may play a role in the treatment and prevention of neurodegenerative diseases, such as Huntington’s, Parkinson’s, and Alzheimer’s disease. For instance, several studies suggest that resveratrol protects neurons from oxidative stressors, toxins, and insults associated with neurodegenerative disorders.

Collectively, these observations strongly suggest that resveratrol can protect against cerebral vascularization defects and then improve the decline of cognitive function associated with aging. However, this effect of resveratrol on cognitive impairment associated with blood-brain flow remains to be clarified.

Low-dose long-term resveratrol reaps rewards in aging rodents

In this work, Garrigue and colleagues explored for the first time whether a low dose of resveratrol can improve cognition in naturally aging rats. The French research team then looked to boil this down to improvements in brain blood flow and the activity of genes implicated in inflammation and oxidative stress-related pathways.

The Aix Marseille University research team investigated the long-term effect of resveratrol treatment on cognitive performances associated with the blood flow in the brains of aged rats. Garrigue and colleagues investigated the effect of long-term resveratrol treatment on cognitive performances of animals that were allowed to age normally. Then, they further analyzed the levels of gene activity and cerebral blood flow in the brain.

Using a novel object recognition test, which evaluates cognition — particularly recognition memory — in rodent models of neurological disorders, the French research team observed that resveratrol enhanced novel object recognition performances of aged rats. “In our study, chronic resveratrol treatment in 6-month-aged rats for 5 months resulted in enhanced performances in the novel object recognition test, translating a gain on non-spatial working memory and exploratory capacities compared to control animals,” concluded Garrigue and colleagues.

In addition, resveratrol enhanced cerebral blood flow during the novel object recognition task in aged rats. The Aix Marseille University researchers also showed that several pathways related to inflammation and oxidative stress were down-regulated in the brains of resveratrol-treated rats compared to untreated, control rats.

Can resveratrol restore aging human brains?

Translation of these findings to humans seems promising, as a recent clinical study including 80 post-menopausal women aged 45 to 85 years notably showed that a 14-week, daily 150 mg resveratrol treatment significantly enhanced both cerebrovascular function and cognition. However, to date, no other published clinical study focused in elder patients and evaluated its effects on cerebral blood flow or cognition. 

References: 

Garrigue P, Mounien L, Champion S, et al. Long-term administration of resveratrol at low doses improves neurocognitive performance as well as cerebral blood flow and modulates the inflammatory pathways in the brain [published online ahead of print, 2021 May 31]. J Nutr Biochem. 2021;108786. doi:10.1016/j.jnutbio.2021.108786