Dose-dependent neuroprotection by 17Betta-estradiol following MPTP intoxication in male mice:role of the neuroinBetta ammatory reaction in estrogen-mediated neuroprotection

• Autorzy: Ciesielska A. , Joniec I. , Cudna A. , Kurkowska-Jastrzebska I. , Zaremba M. , Czlonkowska A.
• Języki publikacji: EN

Abstrakty

EN

17β-estradiol (E2) have been shown to reduce damage of the nigrostriatal system following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The immunosuppressive properties of this hormone may be involved in estrogen-mediated nigro-striatal neuroprotection. We studied the chronic effects of two doses of E2: 0.25 and 2.5 mg per pellet (21-days release) administered 7 days prior MPTP treatment in C57BL male mice (12 months old) on MPTP-induced dopaminergic neurons degeneration and infl ammatory reaction in nigrostriatal pathway. We estimated striatal: tyrosine hydroxylase (TH) and dopamine (DA) level; glial fi brillary acidic protein (GFAP), cytokines (IL-1β, IL-6, TNFα, TGFβ1, IFNg), trophic factor (GDNF) and adhesion molecules (ICAM-1 and VCAM-1) gene expression at 1,7 and 21 days post MPTP intoxication. We showed that only the lower E2 dose (0.25 mg) exerted a neuroprotective effect upon nigrostriatal system. E2 0.25 pre-treatment attenuated the MPTP-induced loss of striatal DA at 1 day time-point and TH at 7- and 21-day time-points. E2 0.25 also diminished the early MPTP-induced increase of the striatal IFNg, IL-1β, TGFβ, ICAM-1, VCAM-1 and GFAP levels but failed to suppress the MPTP-induced increase of striatal TNFα. E2 0.25 also induced an increase of the striatal GDNF and IL-6 gene expression. In contrast, higher E2 doses did not affect the expression of the investigated infl ammatory mediators, expect the GFAP gene expression (increase of the GFAP expression after E2 2.5 administration). We conclude that E2 has a critical dosing effect on dopaminergic neurons survival, only physiologic levels of E2 are neuroprotective in male mice. The neuroprotective effects of E2 might mediate through a modulation of molecular factors of neuroinfl ammatory reaction.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.87

Twórcy

autor

Ciesielska A.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland
• Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland

autor

Joniec I.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland

autor

Cudna A.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland

autor

Kurkowska-Jastrzebska I.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland
• Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland

autor

Zaremba M.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland

autor

Czlonkowska A.

• Department of Experimental and Clinical Pharmacology, Warsaw Medical University, Warsaw, Poland
• Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland