Treatment with resveratrol, a polyphenol found in the skin of red grapes, red wine, peanuts and some berries, results in changes in the hippocampus area of the brain that have apparent benefits in terms of learning, memory and mood function in aged rats.

Resveratrol treatment had positive effects on spatial learning and memory and neurogenesis or addition of new neurons, in the hippocampus. These are the major findings of a study published on January 28th in the journal, Scientific Reports (Nature Publishing). This study is from the research group led by Dr Ashok K. Shetty, Professor and Director of Neurosciences at the Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine in Texas. These findings have implications for potential applications of resveratrol for improving memory and mood function in the elderly population.



The hippocampus is critical to functions including memory, learning and mood, which show mild to moderate deficiency in most people in old age and more extreme impairment in people afflicted with neurodegenerative conditions such as Alzheimer’s disease, Dr. Shetty told SciGuru.org. Aging is also associated with decreased neurogenesis in the dentate gyrus region of the hippocampus. New neurons in this region have been implicated in memory and mood function in adulthood and theories concerning the importance of declining neurogenesis in reduced memory and mood function in aging are increasingly accepted. Other aging-associated changes in the hippocampus include reduced microvasculature, resulting in decreased blood supply and chronic low level inflammation, reflected in astrocyte hypertrophy and activation of microglia, the main immune cells of the brain.



Resveratrol has been associated with antioxidant, anti-inflammatory, anticancer and angiogenic effects, as well as with increased longevity in animal studies. It crosses the blood brain barrier and has been shown to have antidepressant effects in an animal model. A recent clinical study has shown positive effects on memory performance, functional connectivity of the hippocampus and glucose metabolism in healthy older adults, Dr. Shetty noted.



Resveratrol treatment enhances neurogenesis in the aged hippocampus. Left, hippocampus of an aged rat that received vehicle; Right, hippocampus of an aged rat that received resveratrol

Given these effects of resveratrol, the research team in the current study used rats in late middle age to determine the effects of intraperitoneal resveratrol on both spatial learning and memory and on neurogenesis, microvasculature, astrocyte hypertrophy and microglial activation in the hippocampus. Rats in late middle age (21 months old) were matched for spatial learning and memory on the basis of water maze tests and were divided into two groups. One group of eight rats received daily injections of resveratrol for four weeks in their 23rd month while the other control group of seven rats received vehicle injections not containing the resveratrol. When these rats reached 25th month of age, water maze tests for spatial learning and memory were again performed on the aged rats along with forced swim tests, for assessment of depressive-like behaviour. Neurogenesis of the hippocampus was also measured using staining with bromodeoxyuridine for newly born cells, or doublecortin for measurement of more sustained neurogenesis, and NeuN as a marker of neurons. Microvasculature, astrocyte hypertrophy and microglial activation were also assessed with appropriate immunostaining methods.



The results of the study were striking. They indicated that for the control rats who did not receive resveratrol, spatial learning ability was largely maintained but ability to make new spatial memories had significantly declined between 22 and 25 months. By contrast, for the resveratrol-treated rats both spatial learning and memory had improved. Furthermore, the time spent immobile in a forced swim test, a measure of depressive-like behaviour, was significantly less in the resveratrol-treated compared to the control rats. With respect to the hippocampal measurements, resveratrol promoted neurogenesis in the aged rats over a prolonged period; net neurogenesis was approximately doubled compared to the control rats. The resveratrol-treated rats also had significantly improved microvasculature, indicating improved blood flow, compared to the control rats. They also had a lower level of chronic inflammation in the hippocampus, indicated by less astrocyte hypertrophy and less microglial activation.



These results indicated that there were improvements in memory, learning and mood functions in the resveratrol-treated rats which were reflected in significantly increased hippocampal neurogenesis and modification of low-level chronic inflammation. The study authors conclude that the study provides ‘novel evidence that resveratrol treatment in late middle-age is efficacious for improving memory and mood function in old age.’