Parkinson modeli oluşturulmuş sıçanlarda ozon tedavisinin etkisinin biyokimyasal biyobelirteçler ile araştırılması
Proje no. 20564 · Durum: Kapanmış · 2019
Özet
Parkinson's disease (PD) is one of the neurodegenerative diseases that are characterized by the progressive loss of neurons in specific regions of the brain and the entire nervous system, and is defined as a disease whose effects last for years, leading to severe memory loss and severe physical dysfunction in the patient in advanced stages. It is difficult to prove the relationship of many symptoms related to systemic dysfunctions, which is called the presymptomatic stage, which were seen years before the emergence of clinical symptoms due to dopamine deficiency in the substantia nigra in the brain, actually caused by the disease and could offer us early treatment options. PD involves progressive degeneration in the nigrostriatal dopaminergic pathway with significant loss of neurons in the Substantia Nigra pars compacta (SNpc), where dopamine is produced in the brain. Distinctive features in PD pathophysiology are ?-synuclein aggregations in the form of Lewy bodies (LC) and Lewy neurites (LN). It has been understood that PD is indirectly releated with an increase in amyloid- ß level and elevated amyloid-ß plaques, and Tau protein is highly phosphorylated in PD pathology. In addition, it is known that the tyrosine hydroxylase content of neurons decreases and the number of glial cells in the tissue increases in PD pathology. The role of nNOS in the pathogenesis of PD is not fully understood; in some studies no relationship was found between the development of PD and nNOS activity, but in some others, nNOS activity was risen with the development of PD. There is not an effective treatment strategy for the therapy of PD. Side effects of current therapies are harmful for patients and they reduces the quality of life. It is need to have different approaches for a novel therapy of PD and also ?-synuclein protein emerges as a treatment target. In addition, there is no biomarker that provides early diagnosis and follow-up of PD. In this study, we aimed to investigate whether these proteins could be biomarkers in the early diagnosis and follow-up of PD by measuring the levels of some proteins known to be involved in the pathophysiology of PH in both brain tissue and blood, and also to investigate the effectiveness of ozone administration in the treatment of PD. Biochemical analysis (?-synuclein amyloid-ß, Tau, phosphorylated Tau) and histological examinations (?-synuclein, glia cell number, tyrosine hydroxylase (+) cell number, nNOS (+) cell number) were performed of the brain tissues obtained from experimental rats with PD that was treated with intarperitoneal 0.8 mg / kg ozone for 3 weeks (3 times a week) after conducting behavioral tests (apomorphine-induced rotation test) to control the formation of the experimental model in the group of PD experimental model that was developed by rotenone. In addition, blood levels of ?-synuclein, amyloid-ß, Tau, phosphorylated Tau were measured.The apomorphine-induced rotation test was positive in the group of PD experimental model. In histological analyzes in this group, a significant (p <0.05) increase in the number of glia cells in the brain tissue and a significant decrease (p<0,05) in the number of tyrosine hydroxylase (+) cells were found. In addition, high ?-synuclein, amyloid-ß, Tau, phosphorylate Tau levels in brain tissue and blood ?-synuclein were found to be significantly higher (p <0.05) in biochemical analysis. In the histological analysis performed after rats that are experimental model of PD were treated with ozone, tyrosine hydroxylase (+) cell number in brain tissue increased significantly (p <0.05), nNOS (+) and glia cell number decreased significantly. Biochemical analyzes showed that there was a significant decrease of ?-synuclein levels in brain tissue and blood in this group. In conclusion, ozone treatment to PD experimental model altered the level of proteins in the pathophysiology of PD, decreased ?-synuclein levels, increased tyrosine hydroxylase levels, and decreased glia levels this result suggest that of ozone therapy can be an option for PD treatment. We also think that these experimental study results will lead to clinical studies. In addition, since the blood ?-synuclein level is high in the PD model, this protein can be clinically considered as a biomarker that can be used in the early diagnosis and monitoring of PD. To strengthen these results, further research is needed for both optimization of ozone dose and duration of the ozone therapy, as well as clinical studies.