Parkinson Hastalığı Sıçan Modelinde Motor Aktivite ve İnflamatuvar Sürecin Epigallokateşin Gallat ile Modülasyonu

Abstract

Parkinson's disease (PD) is a common degenerative disease of the central nervous system. As, there is no cure for the disease currently, and the drugs used for symptomatic improvement neither prevent the progression of the disease nor neuronal degeneration, it is crucial to investigate approaches that can prevent development and/or progression of the disease. The catechins which are among the natural constituents of tea, one of the most frequently consumed beverages following water all over the world, reduce proinflammatory cytokines and regulate peripheral immunity in PD models. We aimed to investigate the effect of epigallocatechin gallat (EGCG), one of the catechin subspecies, on the development of PD and inflammatory response when applied before or after the application of PD model in rats, in addition to the role of the complement system in neuroinflammation and its modulation by EGCG. The animals which underwent PD model with 6-hydroxydopamine were allocated to PreCatechin (n=10) group which was given 25 mg/kg EGCG p.o. for 5 days before the surgery, PostCatechin (n=11) group which was treated with 25 mg/kg p.o. for 4 days and 10 mg/kg p.o. for the next 10 days after the surgery and P (n=8) group which received only the vehicle. The control groups were sham operated as C group (n=9) and Catechin group (n=10) which received either vehicle or catechin at the regimen and dose applied to the PostCatechin group. Before and 14 days after the surgery motor tests were performed. PD was verified with motor scores and apomorphine tests. The animals were sacrificed after the experimental protocol is completed and blood samples were collected for leucocyte, neutrophil and lymphocyte counts and serum IL1-b and TNF a measurements. The amounts of complement components, C3, CR3 and MAC proteins, were determined from brain tissues. Brain slices were stained by tyrosine hydroxylase immunohistochemically. The decreased dopaminergic neurons in P group, became closer to control groups in EGCG treated animals. The results of motor tests indicated decrease in motor activity, duration on the rotarod and the parameters of horizontal rod test in P group (p<0.05). The EGCGtreated groups were also worse than the sham-operated groups (p<0.05), but exhibited improvement compared to P group (p<0.05). The increased PMN/lymphocyte ratio in P group was lowered with EGCG treatment (p<0.05). The IL1-b and TNF a levels were lower than P group in pre-and post-catechin groups (p<0,05). As a result, our results showed that catechin improved the motor symptoms of PD when administered pre or postphylactically, reduced peripheral inflammation and attenuated neurodegeneration. The investigation of the potential effects and mechanisms of catechins may provide insights especially about the progression of PD.