title: Implication of GPER1 in neuroprotection in a mouse model of Parkinson's disease.
abstract: This study investigated the contribution of the new G protein-coupled estrogen receptor 1 (GPER1) in neuroprotection by 17β-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 17β-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 17β-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 17β-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 17β-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 17β-estradiol in mediating beneficial effects.
authors: Molecular Endocrinology and Genomic Research Center, Centre de recherche du CHUQ (CHUL), Quebec City, Quebec, Canada.
authors: Mélanie
authors: M
authors: Bourque
authors: Marc
authors: M
authors: Morissette
authors: Mélissa
authors: M
authors: Côté
authors: Denis
authors: D
authors: Soulet
authors: Thérèse
authors: T
authors: Di Paolo
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020734:Parkinsonian Disorders / Q000378:metabolism*; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C532507:GPER1 protein, mouse; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D004958:Estradiol; D004298:Dopamine