Impact of food-derived polyphenols on dopamine neurons in the aged brain - 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.
