The neuroprotective action of 17β-estradiol (E2) against 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown in both female and male mice, however the exact mechanisms of that phenomenon remain obscured. We studied the chronic effects of E2 (0.25 mg per pellet, 21-days release) administered 7 days prior (Experiment 1) to or 3 days after (Experiment 2) MPTP intoxication (40 mg/kg, i.p.) in C57BL aged male mice on neurodegenerative and infl ammatory processes in nigrostriatal pathway. We estimated striatal: tyrosine hydroxylase (TH), glial fi brillary acidic protein (GFAP) content (Western blotting); cytokines (TNFα, TGFβ1, IFNγ), trophic factor (GDNF) gene expression (RT-PCR); CD4+ and CD8+ cells infl ux (immunohistochemistry) at 1, 7, 21 (Exp. 1) and 7, 21 (Exp. 2) days post intoxication. E2 exerted a neuroprotective effect upon nigrostriatal system when administered prior but also when administered after intoxication (E2 attenuated the MPTP-induced loss of TH). E2 also decreased the GFAP content. MPTP caused a rapid increase of TGFβ1, TNFα and IFNγ. Pre-treatment with E2 decreased the early expression of TGFβ1 and IFNγ but failed to suppress the MPTP-induced increase of TNFα. E2 pre-treatment also induced an increase of the GDNF and CD4+ cells infl ux to the injured brain areas but decreased the CD8+ cells infi ltration. The neuroprotective effects of E2 indicated in MPTP model might mediate through a modulation of neuroinfl ammatory reaction in lesioned nigrostriatal system.
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