Effects of experimental diabetes on cerebellar CREB / BDNF pathways and motor function

Diabetes mellitus (DM) is a chronic disease with high mortality and morbidity risks. It is well documented that diabetes-related alteration of the central nervous system increases the risk of neurobehavioral disturbances and locomotor disruption. Cerebellum plays a key role in coordination of movements and performing of the motor functions in the body. Cyclic AMP Regulatory Element Binding Protein (CREB) / Brain-derived neurotrophic factor (BDNF) pathway plays a role in the regulation of various functions in the brain such as learning, memory, mood balances and reward mechanisms. Studies have shown that chronic diseases such as DM may impair the CREB / BDNF pathway and cause neurodegeneration. The CREB / BDNF pathway DM was studied in the brain, especially in the hippocampus and other regions of the brain, but the cerebellum pathway was not fully investigated. Complex pathophysiological mechanisms such as oxidative stress have been shown to play a role in neuronal cell damage associated with diabetes mellitus. The possible harmful effects of experimental diabetes on the cerebellum are not understood well. The aim of this study was to investigate the effects of experimentally induced diabetes on cerebellum, how diabetes affects cerebellar motor function and to investigate the effect of diabetes on oxidative stress parameters and CREB / BDNF proteins. In our study, 24 male Wistar Albino rats weighing 300-350 g were randomly divided into two groups. 1) Control group 2) Diabetic group. Streptozotocin (STZ) was administered intraperitoneally as a single dose (60 mg/kg) to induce DM. After 3 days of STZ administration, fasting blood glucose level> 250 mg / kg was accepted as diabetes. The beam walking test (Beam Walking test) was applied to assess motor coordination in animals before the experiment was terminated. Cerebellum tissues were collected from the sacrificed rats and the levels of CREB and BDNF protein were measured by ELISA. Malondialdehyde (MDA) levels and glutathione (GSH) levels as an antioxidant indicator were also measured in terms of lipid peroxidation. The time to complete the platform was lower in the diabetes group compared to the control group in the beam walking test (p <0.05). The levels of BDNF in cerebellum were significantly lower in the diabetic group than in the control group (p <0.05). Cerebellum CREB levels do not differ significantly between diabetic and control groups. MDA levels were significantly higher in the diabetes group than in the control group in the cerebellum (p <0.05). Although cerebellum GSH levels were low in the diabetes group, there was no significant difference between the two groups. This study showed that diabetes reduces the levels of BDNF in the cerebellum and increases distortion of motor functions by increasing oxidative stress.