Dürdane Aksoy1, Volkan Solmaz2, Türker Çavuşoğlu3, Ayfer Meral4, Utku Ateş5, Oytun Erbaş6. 1. Department of Neurology, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey. Electronic address: dbekar@yahoo.com. 2. Department of Neurology, Trakya University Faculty of Medicine, Edirne, Turkey. 3. Department of Histology and Embryology, Ege University Faculty of Medicine, Izmir, Turkey. 4. Department of Biochemistry, Dumlupınar University Evliya Celebi Education and Research Hospital, Kütahya, Turkey. 5. Department of Histology and Embryology, Bilim University Faculty of Medicine, Istanbul, Turkey. 6. Department of Physiology, Bilim University Faculty of Medicine, Istanbul, Turkey.
Abstract
BACKROUND: Several studies suggest an association between Parkinson's disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon-like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene-environment interactions in PD causation and pathogenesis. Therefore, in this study, the neurochemical, behavioral and histologic effects of exenatide on a rotenone-induced rat model of PD were examined. MATERIALS AND METHODS: Eighteen adult male rats were randomly divided into the following 3 groups (n = 6): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1) and the others received stereotaxical infusion of rotenone (groups 2 and 3). Apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered exenatide for 28 days. RESULTS: Malondialdehyde and tumor necrosis factor alpha levels increased in the rats with PD induced by rotenone, whereas malondialdehyde and tumor necrosis factor alpha levels markedly decreased in the rats treated with exenatide. The apomorphine-induced rotation test scores of exenatide-treated rats were determined to be lower compared with the untreated group. Additionally, treatment with exenatide significantly reduced the loss of dopaminergic neurons in striatum. CONCLUSIONS: These results have shown that exenatide has neuroprotective, anti-inflammatory and antioxidant effects in a rotenone-induced rat model of PD.
BACKROUND: Several studies suggest an association between Parkinson's disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon-like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene-environment interactions in PD causation and pathogenesis. Therefore, in this study, the neurochemical, behavioral and histologic effects of exenatide on a rotenone-induced rat model of PD were examined. MATERIALS AND METHODS: Eighteen adult male rats were randomly divided into the following 3 groups (n = 6): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1) and the others received stereotaxical infusion of rotenone (groups 2 and 3). Apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered exenatide for 28 days. RESULTS:Malondialdehyde and tumor necrosis factor alpha levels increased in the rats with PD induced by rotenone, whereas malondialdehyde and tumor necrosis factor alpha levels markedly decreased in the rats treated with exenatide. The apomorphine-induced rotation test scores of exenatide-treated rats were determined to be lower compared with the untreated group. Additionally, treatment with exenatide significantly reduced the loss of dopaminergic neurons in striatum. CONCLUSIONS: These results have shown that exenatide has neuroprotective, anti-inflammatory and antioxidant effects in a rotenone-induced rat model of PD.