Differences in dopaminergic neuroprotective effects of estrogen during estrous cycle

Previous studies suggest that estrogen treatment protects nigrostriatal dopaminergic neurons, but have not examined whether the changes in estrogen levels during estrous cycle can influence the susceptibility of these neurons to neurotoxins. Here we show that the loss of dopaminergic neurons in the substantia nigra was greater in animals lesioned at diestrus (low estrogen) using 6-hydroxydopamine or buffered iron chloride, when compared with animals lesioned at proestrus (high estrogen). Lesioning at diestrus with 6-hydroxydopamine reduced the striatal dopamine content, whereas the dopamine content was preserved in animals lesioned at proestrus. The density of the dopamine transporter, upon which 6-hydroxydopamine toxicity is dependent, was lower when circulating estrogen was high. These results thus support a neuroprotectory role for estrogen.