Project Number: 1950-51000-070-06
Project Type: Trust

Start Date: Oct 01, 2008
End Date: Sep 30, 2011

Objective:
We hypothesize that walnuts will reverse age-related disturbances in behavior, neuronal functioning, and microglial activation and will test this hypothesis with the following aims: 1) Determine the effects of dietary supplementation with walnuts or walnut components on motor and cognitive function. 2) Determine the efficacy of walnuts or walnut components on reversing the age-associated increase in neuronal vulnerability. 3) Investigate the anti-inflammatory actions of walnuts and walnut components on microglial activation. These studies will serve to characterize the effects of dietary walnut supplementation in aging, focusing on cognitive, behavioral, neuronal, and microglial effects of walnuts. In addition, these studies will examine the neuroprotective effects of individual walnut components in order to determine the efficacy of the whole food versus individual components of walnuts.

Approach:
1) Determine the effects of dietary supplementation with walnuts or walnut components on motor and cognitive function. Walnuts will be supplemented in the diet at 6%, walnut components will be given as a portion of the 6% concentration that they comprise in the whole food. The effects of these diets on age-sensitive motor (probes sensitive to balance, strength, and coordination) and cognitive behaviors (short- and long-term memory) will then be examined in Fischer 344 (F344) rats after 8 weeks of supplementation. 2) Determine the efficacy of walnuts or walnut components on reversing the age-associated increase in neuronal vulnerability. The effects of dietary supplementation with walnuts and walnut components on hippocampal neurogenesis (proliferation and survival of newly born neurons) will be assessed in subjects utilized for Aim 1. Additionally, the effects of walnuts on neuronal stress and protective signaling will be accomplished through the use of a hippocampal cell line. Hippocampal cells will be used to determine if walnuts and walnut components alter neuronal stress and protective signaling pathways which have been reported to be altered in the aging brain. 3) Investigate the anti-inflammatory actions of walnuts and walnut components on microglial activation. Prolonged microglial activation is a hallmark of neurodegenerative disorders as well as normal brain aging. The effects of dietary walnut supplementation on age-associated microglial activation will be quantified in tissues harvested from subjects in Aim 1. Further studies on the molecular mechanisms of the anti-inflammatory properties of walnut oil and walnut components will be undertaken in the BV2 microglial cell line.