Resveratrol increases DAT expression levels in the striatum of female mouse and its effect is mediated by estrogen receptors

Resveratrol (3,4',5-trihydroxystilbene, RSV), a phytoalexins with a stilbene skeleton, exhibits a wide range of biological actions that includes neuroprotective effect against neurodegenerative diseases. In a previous study on RSV neuroprotective effects in mouse Parkinson’s model, we unexpectedly observed an upregulation of DAT in the striatum of female mice treated with RSV. Here we aimed to study in depth the effect of RSV on DAT expression, and additionally to verify the potential involvement of estrogen receptor activation by RSV, according with its striking similarity to the synthetic estrogen diethylstilbestrol. Daily repeated injection of RSV (20 mg/kg i.p.) for four days led, eight days after the first injection of RSV, to a significant increase of DAT protein expression levels in the striatum of female mice as compared to matched control. The same RSV injection protocol was not able to increase DAT levels in the striatum of male mice. Basic DAT levels did not show significant difference linked to sex. The pretreatment with the selective estrogen receptor antagonist ICI 182,780 led to a complete block of RSV effect on striatal DAT protein expression levels, whereas the treatment with ICI 182,780 alone was ineffective. The results achieved clearly show that striatal DAT up-regulation following RSV treatment is mediate by DAT estrogen receptors and indicate that RSV through the DAT regulation can exert beneficial influence in the nigrostriatal system of female mice.