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Estrogen receptors and lesion-induced response of striatal dopamine receptors.

Al Sweidi, S; Morissette, M; Rouillard, C; Di Paolo, T.
Neuroscience; 236: 99-109, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23357113
Neuroprotection by 17ß-estradiol and an estrogen receptor (ER) agonist against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion were shown to implicate protein kinase B (Akt) signaling in mice. In order to evaluate the associated mechanisms, this study compared estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) intact or knockout (KO) and wild-type (WT) C57Bl/6 male mice following MPTP treatment of 7, 9, 11mg/kg and/or 17ß-estradiol. Striatal D1 and D2 dopamine (DA) receptors were measured by autoradiography with the specific ligands [(3)H]-SCH 23390 and [(3)H]-raclopride, respectively and signaling by Western blot for Akt, glycogen synthase kinase 3ß (GSK3ß) and extracellular-regulated signal kinases (ERK1 and ERK2). Control ERKOß mice had lower striatal [(3)H]-SCH 23390 specific binding than WT and ERKOα mice; both KO mice had lower [(3)H]-raclopride specific binding. Striatal D1 receptors decreased with increasing doses of MPTP in correlation with striatal DA concentrations in ERKOα mice and remained unchanged in WT and ERKOß mice. Striatal D2 receptors decreased with increasing doses of MPTP in correlation with striatal DA concentrations in WT and ERKOα mice and increased in ERKOß mice. In MPTP-lesioned mice, 17ß-estradiol treatment increased D1 receptors in ERKOα and ERKOß mice and D2 receptors in WT and ERKOß mice. MPTP did not affect striatal pAkt/Akt and pGSK3ß/GSK3ß levels in WT and ERKOα mice, while in vehicle-treated ERKOß mice these levels were higher and increased with MPTP lesioning. Striatal pERK1/ERK1 and pERK2/ERK2 levels showed to a lesser extent a similar pattern. In conclusion, ERs affected the response of striatal DA receptors to a MPTP lesion and post receptor signaling.
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