Submitted to: Nutritional Neuroscience
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/22/2004
Publication Date: 12/1/2004
Citation: Casadesus, G., Shukitt Hale, B., Stellwagen, H.M., Zhu, X., Lee, H., Smith, M.A., Joseph, J.A. 2004. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutritional Neuroscience, Volume 7 Number 5/6 (October/December 2004), pp.309-316 Interpretive Summary: It used to be thought that shortly after we are born that we had all of neurons that we were going to have throughout life and that no more new ones would be made. Now we know that during normal aging no neurons are lost and new ones are still being made (called neurogenesis) even into old age. However, it appears that the rate slows down. One brain region where this occurs is called the hippocampus, which is a major memory control area. In fact previous research has associated reductions in the rate of hippocampal neurogenesis during aging with declines in memory and cognitive processing, indicating a possible causal relationship. Indeed, a growth factor called insulin growth factor-1 (IGF-1) may activate signals such as extracellular signal regulated kinase (ERK) which controls neurogenesis and ultimately learning and memory processes. Previously, we showed that age-related declines in memory tasks can be improved by antioxidant-rich diets containing blueberries. In this study, to begin to understand the mechanisms responsible for the beneficial effects of blueberries, we assessed changes in hippocampal neurogenesis, activation of IGF-1, and ERK levels in blueberry-supplemented aged animals. The results showed that all of these measurements showed increases in the blueberry-supplemented as compared to control. Importantly, the results showed that these increases were significantly correlated with improvements in spatial memory. Therefore, cognitive improvements afforded by fruits such as blueberries, which are abundant in compounds called polyphenolics, may be regulated by their beneficial effects on hippocampal neurogenesis.
Technical Abstract: During aging, reductions in hippocampal neurogenesis are associated with memory decline indicating a causal relationship. Indeed, insulin-like growth factor-1, a major activator of the extracellular receptor kinase pathway that is central in learning and memory processes, is also a key modulator of hippocampal neurogenesis. Previously, we showed that age-related declines in spatial memory tasks can be improved by antioxidant-rich diets containing blueberries. In this study, to begin to understand the mechanisms responsible for the beneficial effects of blueberries, we assessed changes in hippocampal plasticity parameters such as hippocampal neurogenesis, extracellular receptor kinase activation, and insulin-like growth factor-1 and insulin-like growth factor-1 receptor levels in blueberry-supplemented aged animals. Our results show that all these parameters of hippocampal neuronal plasticity are increased in supplemented animals and aspects such as proliferation, extracellular receptor kinase activation and insulin-like growth factor-1 and insulin-like growth factor-1 receptor levels correlate with improvements in spatial memory. Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity.