Estradiol and brain serotonin reuptake transporter in long-term ovariectomized parkinsonian monkeys

Abstract

This study evaluated the effect of a one month 17β-estradiol treatment on brain serotonin (5-HT) reuptake transporter (SERT) in long-term ovariectomized (OVX) female monkeys (Macaca fascicularis) bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injected directly into the left substantia nigra modeling Parkinson disease (PD). Ovariectomy and MPTP lesion were performed four years before the estrogen treatment to model postmenopausal PD patients. SERT was measured by autoradiography using the radioligand [(3)H]Citalopram. Specific binding to SERT decreased in anterior cerebral cortex, nucleus accumbens, caudate nucleus and putamen on the lesioned side of 17β-estradiol and vehicle-treated monkeys compared to the intact side. In caudate nucleus and putamen the lesioned-induced decrease of [(3)H]Citalopram specific binding was more extensive in anterior and middle than posterior parts. [(3)H]Citalopram specific binding was increased in the cortex anterior cingulate gyrus of monkeys treated with 17β-estradiol in both brain hemispheres and was unchanged in the other brain regions investigated including the raphe nucleus. Positive correlations between [(3)H]Citalopram specific binding and 5-HT as well as 5-HIAA concentrations (reported previously) were obtained in the caudate nucleus and putamen and a negative correlation between SERT binding and 5-HIAA/5-HT concentration ratio suggesting MPTP lesion-induced 5-HT neuronal loss and lower 5-HT neurotransmission controlling and decreasing SERT for homeostasis. 17β-estradiol treatment initiated four years after ovariectomy of monkeys modeling hormonal conditions of post-menopause shows that SERT still displays some responsiveness to estrogens as observed in the anterior cingulate cortex. These results support a role of estrogens in 5-HT activity in PD.