Project Number: 1950-51000-063-09
Project Type: Trust

Start Date: Oct 01, 2003
End Date: Jun 30, 2008

Objective:
Phase I ¿ Determine if pomegranate juice supplementation attenuates specific cognitive and motor deficits normally associated with aging. Determine, using cell models, if the effects observed are the result of increased antioxidant and anti-inflammatory protection. Phase II ¿ Determine if purified polyphenol pomegranate powder (PyP) supplementation attenuates specific cognitive and motor deficits normally associated with aging. Determine, using cell models, if the effects observed are the result of increased antioxidant and anti-inflammatory protection.

Approach:
Phase 1 - Thirty male F344 rats 19 mo of age (Harlan Sprague Dawley, Indianapolis, IN) will be used for these experiments. They will be individually housed, provided food and water ad libitum, and maintained on a 12 hr light/dark cycle. Following a 3 day acclimatization period to the facility, they will be randomly assigned to one of 2 diet groups with 20 animals per group; 1) placebo or 2) PJ (diluted to 50%). All animals will be utilized in compliance with all applicable laws and regulations as well as principles expressed in the National Institutes of Health, USPHS, Guide for the Care and Use of Laboratory Animals. The rats will be fed diets for eight weeks before behavioral testing at 21 months, and subsequent cognitive and motor assessments are undertaken. Weights will be recorded every two weeks and food intakes (over a 48 hour period) will be performed two times during the study. Behavior that will be tested will include Morris water maze and accelerod performance. We will also assess muscarinic (important in cognitive and motor function) receptor sensitivity in these animals by determining both oxotremorine-stimulated dopamine release and carbachol-stimulated GTPase activity. Finally we will test the antioxidant/anti-inflammatory activity of serum obtained from these animals in BV 2 and COS-7 cell models. Phase I activity with Pomegranate juice was completed in 2005. Phase 2 - Forty F344 rats 19 mo of age (Harlan Sprague Dawley, Indianapolis, IN) will be used for these experiments. They will be individually housed, provided food and water ad libitum, and maintained on a 12 hr light/dark cycle. Following a 3 day acclimatization period to the facility, they will be randomly assigned to one of 2 diet groups 1) placebo N=10, 2) PyP (2% of the diet N = 15). All animals will be utilized in compliance with all applicable laws and regulations as well as principles expressed in the National Institutes of Health, USPHS, Guide for the Care and Use of Laboratory Animals. The rats will be fed these diets for eight weeks before behavioral testing at 21 months, and subsequent cognitive and more assessments. Weights will be recorded every two weeks and food intakes (over a 48 hour period) will be performed two times during the study. Behavior will be tested with Morris water maze and accelerod performance. We will also assess antioxidant/anti-inflammatory activity of serum obtained from these animals in BV 2 and COS-7 cell models.