Division of Biochemistry, Fujita Memorial Nanakuri Institute, Fujita Health University, Mie, Japan.
Brain Res. 2011 Oct 6;1416:61-8. doi: 10.1016/j.brainres.2011.08.012. Epub 2011 Aug 12.
Identification of functional molecules in the brain related to improvement of the degree of paralysis or increase of activities will contribute to establishing a new treatment strategy for stroke rehabilitation. Hence, protein expression changes in the cerebral cortex of rat groups with/without voluntary exercise using a running wheel after cerebral infarction were examined in this study. Motor performance measured by the accelerated rotarod test and alteration of protein expression using antibody microarray analysis comprised 725 different antibodies in the cerebral cortex adjacent to infarction area were examined. In behavioral evaluation, the mean latency until falling from the rotating rod in the group with voluntary exercise for five days was significantly longer than that in the group without voluntary exercise. In protein expression profile, fifteen proteins showed significant quantitative changes after voluntary exercise for five days compared to rats without exercise. Up-regulated proteins were involved in protein phosphorylation, stress response, cell structure and motility, DNA replication and neurogenesis (11 proteins). In contrast, down-regulated proteins were related to apoptosis, cell adhesion and proteolysis (4 proteins). Additional protein expression analysis showed that both growth-associated protein 43 (GAP43) and phosphorylated serine41 GAP43 (pSer41-GAP43) were significantly increased. These protein expression changes may be related to the underlying mechanisms of exercise-induced paralysis recovery, that is, neurite formation, and remodeling of synaptic connections may be through the interaction of NGF, calmodulin, PKC and GAP43. In the present study at least some of the participation of modulators associated with the improvement of paralysis might be detected.
鉴定与瘫痪程度改善或活动增加相关的大脑功能分子,将有助于建立中风康复的新治疗策略。因此,本研究检查了脑梗死大鼠在使用跑轮进行自愿运动后大脑皮层的蛋白质表达变化。使用抗体微阵列分析,对大脑皮层的运动表现(通过加速转棒测试测量)和蛋白质表达的变化(包含 725 种不同的抗体)进行了检查。在行为评估中,与未进行自愿运动的大鼠相比,进行了 5 天自愿运动的大鼠从旋转杆上掉落的平均潜伏期明显更长。在蛋白质表达谱中,与未进行运动的大鼠相比,15 种蛋白质在进行 5 天自愿运动后出现了明显的定量变化。上调的蛋白质涉及蛋白质磷酸化、应激反应、细胞结构和运动、DNA 复制和神经发生(11 种蛋白质)。相反,下调的蛋白质与细胞凋亡、细胞黏附和蛋白水解(4 种蛋白质)有关。进一步的蛋白质表达分析表明,生长相关蛋白 43(GAP43)和磷酸化丝氨酸 41 GAP43(pSer41-GAP43)均显著增加。这些蛋白质表达的变化可能与运动引起的瘫痪恢复的潜在机制有关,即轴突形成和突触连接的重塑可能是通过 NGF、钙调蛋白、PKC 和 GAP43 的相互作用实现的。在本研究中,至少可以检测到与瘫痪改善相关的一些调节剂的参与。