Recent data indicating that age-related cognitive and motor deficits can be attenuated with the consumption of fruits and vegetables has sparked interest in to whether polyphenols, the chemicals thought to be responsible for these effects, might be effective against Parkinson's disease (PD). Studies using animals of an age typically used in PD research (3-4 months old) have shown that polyphenols/polyphenolic mixtures can protect in various animals models of PD. However, PD is a progressive neurodegenerative disease that predominantly affects the elderly. The brain undergoes a number of changes with aging that may not only affect its vulnerability to damage but also its responsiveness to protective/restorative therapy. We observed that blueberry juice (BBJ) and grapes (GPs) fed to aged rats increased behavioral deficits and damage to the nigrostriatal pathway induced by a dopaminergic neurotoxin coincident with an increase in oxidative stress. No such effects were observed in younger rats. Further pomegranate juice per se was recently shown to increase oxidative stress, inflammation and caspase-3 activation and to potentiate rotenone-induced activation of these same factors in rats. We hypothesize that polyphenols contained within these foods/juices mediate these effects. However, BBJ, GPs and pomegranate juice are all complex mixtures, which in addition to polyphenols contain carbohydrates, vitamins, minerals, and potentially residual levels of herbicides and pesticides as well. Therefore, at present we cannot conclusively link polyphenols to our effects observed with BBJ and GPs. To circumvent this problem, we plan to explore the following aims:
Aim 1 : Formulate synthetic BBJ and assess the distribution of key phenolic compounds in brain tissue. Key components of the commercial BBJ (i.e. flavonoids, phenolic acids and stilbenes) will be assessed using high performance liquid chromatography coupled with high-resolution mass spectrometry (LCMS). Data attained from the LCMS analysis will then be used to prepare the synthetic BBJ. The synthetic BBJ will contain 2-3 key phenolic compounds from each major chemical class at the same concentrations as the commercial product. The distribution of these key phenolic compounds and/or their conjugates will be assessed in brain tissue of young and old rats maintained on the two forms of BBJ for 1-4 wks. Plasma levels will also be assessed at these time points.
Aim 2 : Compare the effect of the two BBJ mixtures in an animal model of PD using young and old rats. The effect of the BBJ mixtures on the vulnerability of nigrostriatal dopamine neurons will be assessed. A battery of sensorimotor behavioral tests will assess the functional effects of maintaining the rats on the two juice mixtures both before and after being challenged with 6-OHDA. Routine immunohistochemical analysis of the striatum and SN coupled with densitometric measures and cell counting will assess the extent of damage to the nigrostriatal pathway.
Media reports touting the age-related health benefits derived from polyphenol-rich foods may help to explain the increased consumption of these foods or their derived beverages. Data are emerging, however, that suggest these food/beverages have the potential to hasten degeneration and increase motor dysfunction in Parkinson's disease (PD). This proposal is designed to establish a causal link between polyphenols contained within fruits and exacerbation of motor dysfunction and cell death in aged animals undergoing progressive degeneration of the brain region responsible for the motor dysfunctions in PD.
