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영어

We investigated the effects of regular treadmill exercise for 6 weeks on NGF, tyrosine kinase receptor A(TrkA), p75 receptor, phosphatidylinositol 3-kinase(PI3-K), mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase 1/2(Erk1/2), cyclic AMP response element-binding protein(CREB), and caspase-3 protein levels in the hippocampus of diabetic rats; we also assessed cell survival and cognitive function. Forty male Sprague-Dawley(SD) rats were divided into four groups: (1) normal control group(NCG: n ＝ 10); (2) normal exercise group(NEG: n ＝ 10); (3) diabetes control group(DCG: n ＝ 10), and (4) diabetes exercise group(DEG: n ＝ 10). Diabetes was induced by injecting streptozotocin(STZ; 55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5, i.p.) into rats. Rats were subjected to treadmill exercise for 5 days a week over 6 weeks, and the speed of the treadmill was gradually increased. In a passive avoidance test, the retention latency in the DCG was significantly shorter than that in the DEG(p < 0.05). Increased BrdU-labeled cells(p < 0.001) and significant increases in NGF and TrkA protein levels were observed in the hippocampal dentate gyrus in the NEG and DEG(p < 0.001 and p < 0.01, respectively). The p75 receptor protein level significantly increased in the NEG but decreased in the DCG(p < 0.001). The p-PI3-K and t-CREB protein levels significantly increased in the NEG(p < 0.001 and p < 0.05, respectively), whereas t-Erk1/2 significantly decreased in the DCG(p < 0.01, p < 0.01, respectively). p-Erk1/2 and p-CREB protein levels significantly increased in the NEG and DEG(p < 0.001, p < 0.001, and p < 0.01, respectively). Caspase-3 protein levels significantly increased in the DCG(p < 0.001). These results show that treadmill exercise improves cognitive function, increases the number of BrdU-labeled cells, and increases NGF levels, by the activation of the MAPK/Erk1/2 signaling pathway in the hippocampus of diabetic rats.