KRONİK EKSİTOTOKSİSİTE MODELİNDE RESVERATROL VE MYRİCETİN'İN MEMBRAN LİPİD PROFİLİ ÜZERİNE ETKİLERİ
Project no. 20670 · Status: Kapanmış · 2019
Summary
Considering the mechanism of neurodegenerative diseases in the nervous system involving neuronal-glial interaction; A complex map emerges in which glutamate excitotoxicity increases oxidative stress and these pathways lead to protein production disorders, aggregation, and therefore membrane lipid dysfunctions, which are closely related to proteins. The leading positions of oxidative stress and glutamate excitotoxicity in these cascades have paved the way for research into designing therapeutic modalities targeting these factors. Resveratrol is a well-researched polyphenol with antioxidant and inhibitory effects on glutamate excitotoxicity and neuroprotective effects. Myricetin, on the other hand, is a flavonoid with stronger antioxidant properties than resveratrol, but its effects and mechanisms on neurons and glia are not understood. In our study, we briefly examined the protective effect of resveratrol and myricetin at various doses in primary neuron culture, primary glia culture, and organotypic brain/hippocampal section cultures in which excitotoxicity was created by glutamate, and the changes in the lipid profile by high-performance liquid chromatography (HPLC) method, together with the results we found. interpreted. Based on the results of our study; in addition to the glutamate-induced excitotoxicity model, lipid profile changes at different rates were observed with the agent drugs we used. Although resveratrol and myricetin seem to have protective effects on cells, it is clear that further studies are needed on this subject. When we look at the lipid profile, the most important change we saw was the change in cholesterol due to glutamate toxicity. Cholesterol increase was observed in almost all study groups, but it is controversial that myricetin and resveratrol have protective effects against this change. It is predicted that the increase in cholesterol may cause an increase in the inner layer thickness of the lipid membrane and a decrease in the excitability threshold, and it is considered as an important therapeutic target for the future. With this study, a student's scientific knowledge and experiences were reinforced within the scope of the Research Education Program and new research goals were revealed with the results. Keywords: glutamate, excitotoxicity, myricetin, resveratrol, neurodegenerative diseases, membrane lipids, chromatography