MedicalResearch.com Interview with:
Ashok K. Shetty, Ph.D.
Professor and Director of Neurosciences
Institute for Regenerative Medicine and Department of Molecular and Cellular Medicine Texas A&M Health Science Center College of Medicine, Temple, TX Research Career Scientist, Central Texas Veterans Health Care System (CTVHCS), Temple, TX
Medical Research: What is the background for this study?
Prof. Shetty: Hippocampus is a region in the brain important for maintaining functions such as learning, memory and mood. However, this region is highly vulnerable to aging and brain insults. Previous research has shown that diminished function in the dentate gyrus region of the hippocampus is one of the key reasons for memory impairments seen in old age. Dentate gyrus is also one of the few regions in the brain where neural stem cells generate new neurons on a daily basis, also referred to as “adult neurogenesis”. Studies have suggested that a significant fraction of newly born neurons mature, get incorporated into the existing hippocampus circuitry and contribute to learning, formation of new memories, and normal mood. However, with aging, the dentate gyrus shows decreased function with some conspicuous structural changes, which include reduced production of new neurons, diminished microvasculature implying reduced blood flow, and occurrence of hypertrophy of astrocytes and activated microglia, signs of chronic low-level inflammation. Because alterations such as reduced neurogenesis, decreased blood flow and brain inflammation can contribute to memory and mood impairments, the idea that drugs that are efficacious for mitigating these changes may preserve memory and mood function in old age has emerged. Such drugs may be prescribed to the aging population if they are efficacious for maintaining normal cognitive and mood function in old age with no or minimal side effects.
Medical Research: What is the rationale for choosing resveratrol for preventing age-related memory dysfunction in this study?
Prof. Shetty: Administration of resveratrol, a naturally occurring polyphenol found in the skin of red grapes, red wine, peanuts and some berries, appeared suitable for counteracting age-related detrimental changes in the hippocampus. This is because, previous studies have shown that resveratrol has ability to promote the formation of new capillaries (through pro-angiogenic effects) and to suppress oxidative stress and inflammation (via antioxidant and antiinflammatory effects) with no adverse side effects. Other studies have also reported that resveratrol can mediate extension of the life span and delayed onset of age related diseases. More importantly, a recent human study suggested that a reasonably lower dose of resveratrol intake for 26 weeks is good enough to improve memory performance as well as hippocampus functional connectivity in 23 healthy overweight older individuals (Witte et al., J. Neurosci., 34: 7862-7870, 2014).
Medical Research: What are the main findings?
Prof. Shetty: With the above background, we specifically wanted to examine whether resveratrol can prevent age-related memory and mood impairments. Hence, we chose rats that typically exhibit normal memory function until late middle age but show memory impairments in old age. We treated rats exhibiting normal memory function with either vehicle or resveratrol in late middle age. Two months after treatment, we again assessed their ability to make new memories. In animals that did not receive resveratrol, spatial learning ability was maintained but ability to make new spatial memories significantly declined. In contrast, animals that received resveratrol treatment in late middle age exhibited beneficial functional and structural changes. The functional benefits included improved ability for spatial learning, preserved proficiency for making new spatial memory, and alleviation of depressive-like behavior associated with aging. The structural changes comprised increased neurogenesis and microvasculature, and reduced astrocyte hypertrophy and activation of microglia in the hippocampus. In summary, the results suggested that resveratrol therapy in late middle age is beneficial for maintaining normal memory and mood function in old age.
Medical Research: What should clinicians and patients take away from your report?
Prof. Shetty: Our study was performed using an animal model of aging but showed strong results in terms of preventing age-related memory and mood dysfunction with beneficial structural modifications in the hippocampus. The results are also consistent with the recent human study showing that a reasonably lower dose of resveratrol intake for 26 weeks can improve memory performance as well as hippocampus functional connectivity in 23 healthy but overweight older individuals (Witte et al., J. Neurosci., 34: 7862-7870, 2014). Nevertheless, results from a larger clinical trial may be needed before recommending the daily intake of resveratrol as a dietary supplement to people. However, eating food rich in resveratrol would likely be helpful for maintaining good memory.
Medical Research: What recommendations do you have for future research as a result of this study?
Prof. Shetty: First, it will be highly useful to examine the beneficial effects of administration of lower doses of resveratrol for extended periods of time in adulthood and middle age on memory, mood and changes in the brain at structural and circuitry levels in old age, using animal models.
Second, performing larger clinical trials that test the effects of resveratrol intake in healthy adult, middle-aged and older individuals, people exhibiting mild cognitive impairment and those in the early stages of Alzheimer’s disease will be of great value.
Kodali M, Parihar VK, Hattiangady B, Mishra V, Shuai B, Shetty AK (2015) Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation. Scientific Reports, Jan 28;5:8075.
MedicalResearch.com Interview with:, & Ashok K. Shetty, Ph.D. (2015). Resveratrol In Food May Help Maintain Memory and Mood in Function in Old Age MedicalResearch.com