BLUEBERRY SUPPLEMENTATION ENHANCES SIGNALING AND PREVENTS BEHAVIORAL DEFICITS IN ALZHEIMER DISEASE MODEL

Authors: Joseph, James; DENISOVA, NATALIE - HNRCA-TUFTS; ARENDASH, GARY - UNIV OF SOUTH FLORIDA; GORDON, MARCIA - UNIV OF SOUTH FLORIDA; Shukitt-Hale, Barbara; MORGAN, DAVID - UNIV OF SOUTH FLORIDA

Submitted to: Nature Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/14/2003
Publication Date: 5/1/2003
Citation: Joseph, J.A., Arendash, G., Gordon, M., Diamond, D., Shukitt Hale, B., and Morgan, D. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Nutr. Neurosci. 2003, 6: 153-162.

Interpretive Summary: As is well known, animals do not develop Alzheimer Disease. Therefore, over the last several years mouse models have been developed using molecular biological techniques which show similar changes in those seen in various human diseases such as Alzheimer Disease (AD). In these experiments we used an AD mouse model called the APP/PS1 mouse. The name is derived from the mutations that have been made in this mouse that lead to the development of brain pathology consistent with that seen in Alzheimer disease. In this mouse, these changes include the development of numerous small, dark punctate areas in the mouse brain called " amyloid plaques." These plaques are one of the hallmarks of the disease. In this study the mouse were fed a control or a blueberry (BB)-supplemented diet from about 4 mo. of age to 12 months of age., and then tested on a cognitive behavioral task called a Y-maze, in which the animal has to alternate among the three arms of this maze. The results showed that the animals maintained on the BB diet. showed significantly greater performance than that seen in the animals not given this diet. More importantly is the finding that although BB-supplementation did not decrease the brain pathology in these mice it significantly increase the neuronal communication. We postulated that these increases in neuronal communication offset the negative effects of the plaques in the brain. Thus, these findings suggest for the first time that it may be possible to overcome genetic predispositions to AD through diet.

Technical Abstract: Previously, we showed that blueberry supplementation (BBS) reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BBS from 4 months of age in APP+PS1 transgenic mice showed no deficits in Y-maze performance (at 12 mo of age) Blueberry supplementation had a beneficial effect on Y maze performance. where in the non-supplemented transgenic animals exhibited significantly lower percentages of alternation behavior than the non-transgenic animals fed the control diet [t(9) = 2.60, p < 0.05]. Moreover, the results indicated that the behavioral performance of the non-supplemented transgenic animals was lower than that of the BB supplemented transgenic animals [t(4) = 2.93, p < 0.05], and the behavioral performance of the transgenic BB supplemented group did not differ from either of the control groups (p > 0.05) with no reductions in the amyloid beta plaques in the brain alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced increases in memory-associated neuronal signaling in such markers as extracellular signal regulated kinase, (ERK) activity and protein kinase C activity as assessed by Western Blot Analysis. Reductions were seen in Neutral Sphingomyelin-specific PLC (N-Sase) activity (also assessed via Western blot analysis). This marker is associated with increases in the turn over of sphingomyelin which we have shown to increase vulnerability to oxidative stress. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to AD through diet by enhancing neuronal communication and possibly reducing vulnerability to oxidative stress.