Department of Biosciences, São Paulo Federal University (UNIFESP), Santos, São Paulo, Brazil.
Hippocampus. 2014 Jun;24(6):703-11. doi: 10.1002/hipo.22261. Epub 2014 Feb 19.
Diabetes mellitus is a chronic disease that has been associated with memory loss, neurological disorders, and Alzheimer's disease. Some studies show the importance of physical exercise to prevent and minimize various neurological disorders. It is believed that the positive effects of exercise on brain functions are mediated by brain insulin and insulin-like growth factor-1 (IGF-1) signaling. In this study, we investigate the role of swimming exercise training on hippocampus proteins related to insulin/IGF-1 signaling pathway in Type 1 diabetic rats and its effects on spatial memory. Wistar rats were divided into four groups namely sedentary control, trained control, sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, per 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. We employed ALX-induced diabetic rats to explore learning and memory abilities using Morris water maze test. At the end of the training period, the rats were sacrificed 48 h after their last exercise bout when blood samples were collected for serum glucose, insulin, and IGF-1 determinations. Hippocampus was extracted to determinate protein expression (IR, IGF-1R, and APP) and phosphorylation (AKT-1, AKT-2, Tau, and β-amyloide proteins) by Western Blot analysis. All dependent variables were analyzed by two-way analysis of variance with significance level of 5%. Diabetes resulted in hyperglycemia and hypoinsulinemia in both SD and TD groups (P < 0.05); however, in the training-induced group, there was a reduction in blood glucose in TD. The average frequency in finding the platform decreased in SD rats; however, exercise training improved this parameter in TD rats. Aerobic exercise decreased Tau phosphorylation and APP expression, and increased some proteins related to insulin/IGF-1 pathway in hippocampus of diabetic rats. Thus, these molecular adaptations from exercise training might contribute to improved spatial learning and memory in diabetic organisms.
糖尿病是一种慢性疾病，与记忆丧失、神经紊乱和阿尔茨海默病有关。一些研究表明，体育锻炼对于预防和最小化各种神经紊乱至关重要。人们认为，运动对大脑功能的积极影响是通过大脑胰岛素和胰岛素样生长因子-1（IGF-1）信号传导来介导的。在这项研究中，我们研究了游泳运动训练对 1 型糖尿病大鼠海马胰岛素/IGF-1信号通路相关蛋白的作用及其对空间记忆的影响。Wistar 大鼠分为四组：安静对照组、训练对照组、安静糖尿病组（SD）和训练糖尿病组（TD）。糖尿病通过链脲佐菌素（ALX）（32mg/kg b.w.）诱导。训练方案包括每周 5 天、每天 1 小时、共 6 周，支持 90%的无氧阈值的过载。我们使用 ALX 诱导的糖尿病大鼠通过 Morris 水迷宫测试来探索学习和记忆能力。在训练期结束时，大鼠在最后一次运动后 48 小时被处死，采集血样以测定血清葡萄糖、胰岛素和 IGF-1。提取海马以通过 Western Blot 分析测定蛋白质表达（IR、IGF-1R 和 APP）和磷酸化（AKT-1、AKT-2、Tau 和 β-淀粉样蛋白）。所有依赖变量均通过双因素方差分析进行分析，显著水平为 5%。糖尿病导致 SD 和 TD 两组血糖升高和胰岛素水平降低（P<0.05）；然而，在训练诱导组中，TD 组的血糖降低。SD 大鼠找到平台的平均频率降低；然而，运动训练改善了 TD 大鼠的这一参数。有氧运动降低 Tau 磷酸化和 APP 表达，并增加糖尿病大鼠海马中与胰岛素/IGF-1 途径相关的一些蛋白质。因此，运动训练的这些分子适应可能有助于改善糖尿病机体的空间学习和记忆。
