Exercise Training Alleviates Cognitive Functions in Diabetic Rats through HMGB1/RAGE/NF-kB Pathway

Abstract Objective: To observe the effect of exercise training on cognitive functions of diabetic rat model. Methods: Male SD rats were given a high fat and high sugar diet, except for control group. After 4 weeks, 35 mg /kg STZ was intraperitoneally injected to establish type 2 diabetes model rats. After successful modeling, rats were randomly divided into the model group, model + exercise group. Animals performed 5 days of consecutive treadmill exercise (60 min/day) with 22 m/min speeds for 60 days. After 60 days, behavioral tests were conducted by Morris water maze method. then rats were weighed and blood samples were obtained to detect blood glucose. Some animals were sacrificed to prepare serum to detect glycosylated hemoglobin. Brain tissues were taken to detect the protein expressions of HMGB1-/RAGE-/NF-κB signal pathway by Western Blot. The brains of other animals were perfused and taken for RAGE and NF-κB immunohistochemical staining.Results: Compared with control group, escape latency and probe distance in the model group were significantly prolonged, swimming time in the target quadrant was significantly shortened, and the number of crossing platform was significantly reduced. The average grayvalues of NF-κB and RAGE were significantly decreased. Expressions of HMGB1,RAGE,p-NF-кBp65 and p-IкBα were significantly up-regulated(P<0.05 or P<0.01). Compared with the model group, escape latency and probe distance were significantly shortened, swimming time in the target quadrant was prolonged and increased the number of crossing platform, it also reduced the fasting blood glucose, increased body weights, reduced the level of glycated hemoglobin, and significantly increased the mean grayvalues of NF-κB and RAGE. The protein expressions of HMGB1, RAGE, p-NF-кBp65 and p-IкBα were decreased in model + exercise group.Conclusion: Exercise training can ameliorate the cognitive dysfunction of diabetic rats, its mechanism may be related to reducing blood glucose, reducing the level of glycated hemoglobin and improving the HMGB1 /RAGE/NF-κB pathway in the brain tissue.