DIETARY SUPPLEMENTATION WITH BLUEBERRY EXTRACT IMPROVES SURVIVAL OF TRANSPLANTED DOPAMINE NEURONS

Authors: MCGUIRE, SUSAN - LOYOLA UNIV. MED. SCHOOL; SORTWELL, CARYL - RUSH UNIV. MED. CENTER; Shukitt-Hale, Barbara; Joseph, James; HEJNA, MATTHEW - LOYOLA UNIV. MED. SCHOOL; COLLIER, TIMONTHY - RUSH UNIV. MED. CENTER

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2006
Publication Date: 10/24/2006
Citation: Mcguire, S.O., Sortwell, C.E., Shukitt Hale, B., Joseph, J.A., Hejna, M.J., Collier, T.J. 2006. Dietary supplementation with blueberry extract improves survival of transplanted dopamine neurons. Nutritional Neuroscience. 9(5/6): 251-258.

Interpretive Summary: One of the treatments for Parkinson's disease (PD) is to transplant embryonic dopamine (DA) neurons (brain cells)into the area of the brain where there are a lot of cell associated with the disease. However, the newly transplanted cells do not have a high survival rate. Transplanted cells most likely do not survive because of an inflammatory immune reaction in response to the foreign tissue or possibly due to the fact that these cells are highly susceptible to oxidative stress (OS). There have been attempts to pre-treat the cells with antioxidants and anti-inflammatory compounds before implantation, but there has not been much research that attempts to treat the recipient of these cells with the same types of compounds. We hypothesized that feeding PD model rats a diet supplemented with blueberry extract (BBE) would increase the survival rates of the implanted cells because blueberries have high levels of flavonoids, phytochemicals that have been shown to have antioxidant and anti-inflammatory effects. Inclusion of 2% BBE in a custom chow diet significantly increased the survival implanted DA neurons and improved behavior as compared to transplanted animals consuming a standard diet. These findings provide support for the potential of dietary phytochemicals as an easily administered and well-tolerated therapy that can be used to improved the effectiveness of DA neuron replacement.

Technical Abstract: The exact mechanisms contributing to poor neuronal survival in cell transplantation paradigms for Parkinson's disease (PD) are unknown. However, transplantation-induced host immune response and subsequent oxidative stress are likely contributors to cell death since dopamine (DA) neurons are exquisitely sensitive to oxidative damage. Multiple studies have attemped to improve cell survival by pretreating transplant material with antioxidant and antiinflammatory compounds, whereas far fewer studies have attempted to modify the host environment to reduce these threats. Flavonoids, phytochemicals found in fruits and vegetables, have antioxidants, anti-inflammatory, and immunomodulatory properties. For example, dietary blueberry extract (BBE) prevents oxidative stress associated impairment of striatal motor function during aging and restores lost motor function in aged rats. We hypothesized that dietary supplementation with BBE would improve the survival of embryonic DA neurons transplanted into the striatum of young, DA depleted rats. Inclusion of 2% BBE in a custom chow diet significantly increased the survival of implanted DA neurons and ameliorated rotational behavior asymmetries as compared to transplanted animals consuming a standard diet. These findings provide support for the potential of dietary phytochemicals as an easily administered and well-tolerated therapy that can be used to improve the effectiveness of DA neuron replacement.