Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX.
Sleep. 2013 May 1;36(5):751-61. doi: 10.5665/sleep.2642.
The present study aimed to investigate the effects of treadmill exercise on sleep deprivation (S-D)-induced impairment of hippocampal dependent long-term memory, late phase long-term potentiation (L-LTP) and its signaling cascade in the cornu ammonis 1 (CA1) area.
Animals were conditioned to run on treadmills for 4 weeks then deprived of sleep for 24 h using the columns-in-water method. We tested the effect of exercise and/or S-D on behavioral performance using a post-learning paradigm in the radial arm water maze (RAWM) and in vivo extracellular recording in the CA1 area. The levels of L-LTP-related molecules in the CA1 area were then assessed both before and after L-LTP induction.
After 24 h of S-D, spatial long-term memory impairment in the RAWM and L-LTP suppression was prevented by 4 weeks of regular exercise. Regular exercise also restored the S-D-associated decreases in the basal levels of key signaling molecules such as: calcium/calmodulin kinase IV (CaMKIV), mitogen-activated protein kinase (MAPK/ERK), phosphorylated cAMP response element-binding protein (P-CREB) and brain derived neurotrophic factor (BDNF), in the CA1 area. After L-LTP induction, regular exercise also prevented the S-D-induced down regulation of BDNF and P-CREB protein levels.
The results suggest that our exercise protocol may prevent 24-h S-D-induced impairments in long-term memory and LTP by preventing deleterious changes in the basal and post-stimulation levels of P-CREB and BDNF associated with S-D.
本研究旨在探讨跑步机运动对睡眠剥夺(S-D)引起的海马依赖性长时记忆损伤、迟发性长时增强(L-LTP)及其在 CA1 区信号级联的影响。
动物经过 4 周的跑步机训练,然后采用柱水法剥夺 24 小时睡眠。我们使用学习后范式在放射臂水迷宫(RAWM)和 CA1 区体内细胞外记录中测试运动和/或 S-D 对行为表现的影响。然后在 L-LTP 诱导前后评估 CA1 区与 L-LTP 相关的分子水平。
在 S-D 24 小时后,4 周的常规运动可预防 RAWM 中的空间长时记忆损伤和 L-LTP 抑制。常规运动还恢复了 S-D 相关的关键信号分子(如钙/钙调蛋白激酶 IV(CaMKIV)、丝裂原活化蛋白激酶(MAPK/ERK)、磷酸化 cAMP 反应元件结合蛋白(P-CREB)和脑源性神经营养因子(BDNF))在 CA1 区的基础水平降低。在 L-LTP 诱导后,常规运动还可防止 S-D 诱导的 BDNF 和 P-CREB 蛋白水平下调。
结果表明,我们的运动方案可能通过防止与 S-D 相关的 P-CREB 和 BDNF 的基础和刺激后水平的有害变化,预防 24 小时 S-D 引起的长时记忆和 LTP 损伤。