| First Author | Al-Sweidi S | Year | 2011 |
| Journal | Neuropharmacology | Volume | 61 |
| Issue | 4 | Pages | 583-91 |
| PubMed ID | 21586296 | Mgi Jnum | J:178501 |
| Mgi Id | MGI:5298468 | Doi | 10.1016/j.neuropharm.2011.04.031 |
| Citation | Al-Sweidi S, et al. (2011) Estrogen receptors and gonadal steroids in vulnerability and protection of dopamine neurons in a mouse model of Parkinson's disease. Neuropharmacology 61(4):583-91 |
| abstractText | 17beta-estradiol is well known to have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We investigated the neuroprotective contribution of estrogen receptors (ERalpha and ERbeta) against MPTP toxicity by examining the membrane dopamine (DA) transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and tyrosine hydroxylase (TH) in ER knock out (ERKO) C57Bl/6 male mice compared to their plasma steroid levels. A dose-response to MPTP comparing wild-type (WT) to ERKO mice was studied. WT mice were also compared to ERKO mice pretreated with 17beta-estradiol alone and with MPTP. Specific radioligand binding autoradiography and in situ hybridization for DAT, VMAT2 and TH were assayed in the striatum and the substantia nigra (SN). Intact ERKObeta mice had both striatal transporters levels lower than WT and ERKOalpha mice. MPTP caused a dose-dependent loss of both striatal transporters that correlated with striatal DA concentrations. Compared to WT and ERKObeta mice, ERKOalpha mice DAT, VMAT2 and TH were affected at lower MPTP doses. In the striatum and SN, ERKOalpha mice were more vulnerable and 17beta-estradiol protected against MPTP toxicity only in WT mice. ERKOalpha mice blood plasma had higher levels of testosterone, dihydrotestosterone and 3beta-diol compared to the plasma of WT and ERKObeta mice. 17beta-estradiol treatment increased estradiol plasma levels in all genotypes. Striatal DA concentrations and SN TH mRNA correlated inversely with plasma testosterone and 3beta-diol levels. Hence, in male mice the lack of ERalpha or ERbeta altered their basal plasma steroid levels and both striatal DA transporters as well as their susceptibility to MPTP toxicity. |
