Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Instituto Federal Goiano (IF Goiano), Campus Ceres, Ceres, Brazil.
J Neurosci Res. 2018 May;96(5):911-920. doi: 10.1002/jnr.24196. Epub 2017 Nov 2.
There are a considerable number of studies concerning the behavioral effects of physical exercise on the epileptic brain; however, the intracellular signaling mechanisms involved remain unclear. We investigated the effects of aerobic exercise on hippocampal levels of brain-derived neurotrophic factor (BDNF), expression of its receptor tropomyosin receptor kinase B (TrkB), and activation of intracellular proteins related to BDNF-TrkB signaling in male Wistar rats with pilocarpine-induced epilepsy. Thirty days after the first spontaneous seizure, rats from the exercise group undertook a 30-day physical exercise program on the treadmill. Thereafter, BDNF levels, expression of TrkB, and activation of intracellular proteins were quantified by enzyme-linked immunosorbent assay, Western blotting, and multiplex assay, respectively. Statistical analyses were conducted using nonparametric tests. Rats with epilepsy presented decreased BDNF levels compared with control rats. BDNF levels increased significantly in the exercise group compared with the epileptic and control groups. Expression of full-length and truncated TrkB was increased in rats with epilepsy, and physical exercise restored its expression to control levels. RAC-alpha serine/threonine-protein kinase, mammalian target of rapamycin, and extracellular signal-regulated kinase activation were reduced in rats with epilepsy, and exercise increased activation compared with control and epilepsy groups. Increased cAMP response element binding protein activation was observed in the exercise group compared with the epilepsy group. Our findings indicate that the beneficial effects of exercise in the epileptic brain can be in part related to alterations in the activation of proteins related to the BDNF-TrkB signaling pathway.
有相当数量的研究关注体育锻炼对癫痫大脑的行为影响；然而，涉及的细胞内信号机制仍不清楚。我们研究了有氧运动对匹罗卡品诱导癫痫的雄性 Wistar 大鼠海马脑源性神经营养因子 (BDNF) 水平、其受体原肌球蛋白受体激酶 B (TrkB) 表达以及与 BDNF-TrkB 信号相关的细胞内蛋白激活的影响。第一次自发性癫痫发作 30 天后，运动组的大鼠在跑步机上进行了 30 天的运动计划。此后，通过酶联免疫吸附试验、Western blot 和多重分析分别定量 BDNF 水平、TrkB 表达和细胞内蛋白的激活。使用非参数检验进行统计分析。与对照组相比，癫痫大鼠的 BDNF 水平降低。与癫痫组和对照组相比，运动组的 BDNF 水平显著增加。全长和截断型 TrkB 的表达在癫痫大鼠中增加，而运动使其表达恢复到对照水平。癫痫大鼠中 RAC-alpha 丝氨酸/苏氨酸蛋白激酶、哺乳动物雷帕霉素靶蛋白和细胞外信号调节激酶的激活减少，而运动则增加了与对照组和癫痫组相比的激活。与癫痫组相比，运动组 cAMP 反应元件结合蛋白的激活增加。我们的研究结果表明，运动对癫痫大脑的有益影响部分可能与 BDNF-TrkB 信号通路相关蛋白的激活改变有关。
