17 β-Estradiol Oxidative Stress Attenuation and Autophagy-Induced Dopaminergic Neuroprotection
Journal Title: Cell Journal(Yakhteh) - Year 2019, Vol 21, Issue 1
Abstract
Objective Degeneration of dopaminergic neurons in the substantia nigra of the brain stem is the main pathological aspect of Parkinson’s disease (PD). 17 β-estradiol (E2) has neuroprotective effects on substantia nigra, however, the underlined mechanism is not well-known. In this study, we evaluated the neuroprotective effects of E2 in the ovariectomized 6-hydroxydopamine- (6-OHDA) rat model of PD. Materials and Methods In this experimental study, all animals were ovariectomized to avoid any further bias in E2 levels and then these ovariectomized rats were randomly assigned into three experimental groups (10 rats in each group): ovariectomized control group (OCG), ovariectomized degeneration group receiving 25 μg of 6-OHDA into the left corpus striatum (ODG), and ovariectomized E2 pretreatment group pretreated with 0.1 mgkg-1of 17 β-estradiol for three days prior to the destruction of corpus striatum with 6-OHDA (OE2PTG). The apomorphine behavioral test and Nissl staining were performed in all experimental groups. The expressions of Sequestosome-1 (P62), Unc- 51 like autophagy activating kinase (Ulk1), and microtubule-associated proteins 1A/1B light chain 3B (Lc3) genes were evaluated using reverse transcription- polymerase chain reaction (RT-PCR). Results E2 administration reduced the damages to the dopaminergic neurons of the substantia nigra. The motor behavior, the number of rotations, and histological tests in the treatment group showed the cell survival improvement in comparison with the control groups indicating that E2 can inhibit the neurodegeneration. P62 and Lc3 were expressed in all experimental groups while Ulk1 was not expressed in ODG group. Moreover, Ulk1 was expressed after the treatment with E2 in OE2PTG group. Conclusion E2 prevents neurodegeneration in dopaminergic neurons of the midbrain by over-expression of Ulk1 gene and augmenting the induction of autophagy.
Authors and Affiliations
Roya Varmazyar, Ali Noori-Zadeh, Farzad Rajaei, Shahram Darabi, Salar Bakhtiyari
Keywords
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- EP ID EP461186
- DOI 10.22074/cellj.2019.5799
- Views 259
- Downloads 0
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