Implication of GPER1 in neuroprotection in a mouse model of Parkinson's disease

This study investigated the contribution of the new G protein-coupled estrogen receptor 1 (GPER1) in neuroprotection by 17 beta-estradiol in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. In intact mice, administration of GPER1 agonist G1 reproduced the effect of 17 beta-estradiol in increasing striatal dopamine metabolite concentrations as well as the turnover of dopamine. GPER1 antagonist G15 blocked the effect of G1 on homovanillic acid/dopamine ratio and partially for 17 beta-estradiol. MPTP mice treated with G15 were more susceptible to MPTP toxicity with a greater decrease in striatal dopamine concentration and dopamine transporter specific binding. In MPTP mice, dopamine concentrations as well as dopamine and vesicular monoamine transporter 2 specific binding showed that G1 treatment was as potent as 17 beta-estradiol in protecting striatum and substantia nigra. G15 antagonized completely the neuroprotective effects of G1 in the striatum and substantia nigra as well as protection by 17 beta-estradiol in the striatum but partially in the substantia nigra. This study showed an important role of GPER1 in neuroprotection and that G1 is as potent as 17 beta-estradiol in mediating beneficial effects. (C) 2013 Elsevier Inc. All rights reserved.