Effects of green tea polyphenols on dopamine uptake and on MPP+ -induced dopamine neuron injury

As antioxidants, polyphenols are considered to be potentially useful in preventing chronic diseases in man, including Parkinson's disease (PD), a disease involving dopamine (DA) neurons. Our studies have demonstrated that polyphenols extracted from green tea (GT) can inhibit the uptake of 3H-dopamine (3H-DA) and 1-methyl-4-phenylpyridinium (MPP(+)) by DA transporters (DAT) and partially protect embryonic rat mesencephalic dopaminergic (DAergic) neurons from MPP(+)-induced injury. The inhibitory effects of GT polyphenols on 3H-DA uptake were determined in DAT-pCDNA3-transfected Chinese Hamster Ovary (DAT-CHO) cells and in striatal synaptosomes of C57BL/6 mice in vitro and in vivo. The inhibitory effects on 3H-MPP(+) uptake were determined in primary cultures of embryonic rat mesencephalic DAergic cells. Inhibition of uptake for both 3H-DA and 3H-MPP(+) was dose-dependent in the presence of polyphenols. Incubation with 50 microM MPP(+) resulted in a significant loss of tyrosine-hydroxylase (TH)-positive cells in the primary embryonic mesencephalic cultures, while pretreatment with polyphenols (10 to 30 microg/ml) or mazindol (10 microM), a classical DAT inhibitor, significantly attenuated MPP(+)-induced loss of TH-positive cells. These results suggest that GT polyphenols have inhibitory effects on DAT, through which they block MPP(+) uptake and protect DAergic neurons against MPP(+)-induced injury.