Deneysel Parkinson Hastalığı Modelinde Obezitenin Motor Becerilere Etkisi ve Beyin Tirozin Hidroksilaz Düzeyi, Dopaminerjik Reseptörler ve Leptin Reseptörleri ile İlişkisinin İncelenmesi

Abstract

Excessive increase in body weight, which has already become a public health problem, is also associated with many diseases. On the other hand, prolonged life expectancy also increases the incidence of neurodegenerative diseases. Relationship between obesity and Parkinson's disease (PD), which affects the movement-related mechanisms and increases in incidence with advancing age, is not fully known. In this study, we aimed to investigate the relationship between body weight gain and clinical symptoms of PD in animals fed with high-fat diet in terms of tyrosine hydroxylase, D1, D2 receptors and leptin receptor levels in brain sections together with motor function tests. Adult male Sprague Dawley rats were fed either with 30% fat containing high-fat (HFD, n=15) or standard chow (STD, n=15) for 8 weeks. After reaching the desired body weight, PD model was created with stereotaxic injection of 6-hydroxydopamine. Motor tests were performed before and 21 days after the creation of stereotaxic PD model. In addition, on the 21st day after stereotaxic injections, the success in development of PD model in animals was determined with apomorphine, a dopaminergic agonist. Tyrosine hydroxylase, leptin receptor, D1 and D2 dopamine receptors were evaluated by immunofluorescent (IF) staining of brain tissues of the animals. Animals in the HFD group had lower motor scores than the STD group before the stereotaxy application. Difference in motor scores between the HFD and STD groups disappeared after stereotaxy application. Tyrosine hydroxylase density was found to be lower in the intact and denervated hemispheres of the HFD group than in the STD group. The D1 receptor density was also found to be at lower density in both intact and denervated hemispheres of the HFD group. D2 receptor density was found to be higher in staining intensity for the denervated hemisphere than intact hemisphere for the STD group. The leptin receptor density was found to be at higher density in both hemispheres for the HFD group than for the STD group. As a result, the relationship between body weight gain and clinical symptoms of PD in animals fed with HFD is affected by dopamine and leptin receptor levels. Further examination of intracellular signalling cascades and interactions with other adipokines can help to elucidate the possible links between obesity and PD.