Browsing by Author "Bernardino, Ana Carolina de Matos"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- Evaluation of the antioxidant action of the G protein-coupled estrogen receptorPublication . Bernardino, Ana Carolina de Matos; Baltazar, Graça Maria FernandesThe brain is characterized by a high metabolism and contains several easily oxidizable substances such as amines and lipids, resulting in exposure to high levels of oxidative stress. In Parkinson's disease (PD), oxidative stress has been shown to be correlated with lipid peroxidation, inflammation, mitochondrial dysfunction and aggregation of a-synuclein (asyn). This demonstrates that oxidative stress can be one of the triggers of Parkinson's disease, as it is capable of inducing a series of pathogenic mechanisms characteristic of the disease, contributing to its progression. In this sense, the identification of mechanisms that help reducing oxidative stress may be an interesting strategy for controlling the progression of the disease. Since 17ß-estradiol exerts neuroprotective functions and has proved beneficial effects on several mechanisms such as neuroinflammation, excitotoxicity, among others, we assessed whether the selective activation of the G protein-coupled estrogen receptor (GPER), characterized by being involved in rapid non-genomic actions of 17ßestradiol, can exert a neuroprotective effect associated with the modulation of oxidative stress. With this objective, we developed an in vivo study with mice injected with 6-OHDA, which were later submitted to subcutaneous or intranasal treatment with the GPER agonist, G1. We evaluated how the selective activation of the receptor can contribute to the reversion of oxidative stress. To this end, several behavioral tests were performed to evaluate motor function, such as Grip Test, Rotarod and Open Field Test, and relative mRNA levels of antioxidant enzymes were measured by real-time PCR (RT-PCR). From the behavioral tests, it was possible to conclude that the 6-OHDA-injection was not capable of affecting motor behavior, since the results obtained with the Rotarod test, and the total distance travelled obtained with the Open field Test did not present significant differences. On the other hand, it was possible to observe that the parameters related with anxious behavior were increased in animals injected with 6-OHDA, when compared with the control group. Therefore, it can be concluded that the toxin had no effect at the level of motor behavior, but induced changes in non-motor domains. Regarding the expression of antioxidant enzymes, although not significant, an increase in the mRNA levels of Gpx4 and Nrf2 was observed in 6-OHDAinjected mice. This increase suggests a protective mechanism aiming to limit oxidative stress. However, further studies are needed to confirm this hypothesis. Our results have shown effects exercised by the G1, when administered by the two delivery approaches. However, it was not possible to conclude whether the two types of G1 delivery have an antioxidant effect in the presence of a dopaminergic insult. In this sense, further studies would be necessary to confirm whether GPER activation is capable of modulating oxidative stress and whether this effect is related to its currently recognized neuroprotective effects.