Zagaar Munder A, Dao An T, Alhaider Ibrahim A, Alkadhi Karim A
Departmentof Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA.
College of Clinical Pharmacy, King Faisal University, Al-Hofuf, Saudi Arabia.
Mol Neurobiol. 2016 Jul;53(5):2900-2910. doi: 10.1007/s12035-015-9176-4. Epub 2015 Apr 23.
The dentate gyrus (DG) and CA1 regions of the hippocampus are intimately related physically and functionally, yet they react differently to insults. The purpose of this study was to determine the protective effects of regular treadmill exercise on late phase long-term potentiation (L-LTP) and its signaling cascade in the DG region of the hippocampus of rapid eye movement (REM) sleep-deprived rats. Adult Wistar rats ran on treadmills for 4 weeks then were acutely sleep deprived for 24 h using the modified multiple platform method. After sleep deprivation, the rats were anesthetized and L-LTP was induced in the DG region. Extracellular field potentials from the DG were recorded in vivo, and levels of L-LTP-related signaling proteins were assessed both before and after L-LTP expression using immunoblot analysis. Sleep deprivation reduced the basal levels of phosphorylated cAMP response element-binding protein (P-CREB) as well as other upstream modulators including calcium/calmodulin kinase IV (CaMKIV) and brain-derived neurotrophic factor (BDNF) in the DG of the hippocampus. Regular exercise prevented impairment of the basal levels of P-CREB and total CREB as well as those of CaMKIV in sleep-deprived animals. Furthermore, regular exercise prevented sleep deprivation-induced inhibition of L-LTP and post-L-LTP downregulation of P-CREB and BDNF levels in the DG. The current findings show that our exercise regimen prevents sleep deprivation-induced deficits in L-LTP as well as the basal and poststimulation levels of key signaling molecules.
海马体的齿状回（DG）和CA1区域在生理和功能上密切相关，但它们对损伤的反应不同。本研究的目的是确定定期跑步机运动对快速眼动（REM）睡眠剥夺大鼠海马体DG区域晚期长时程增强（L-LTP）及其信号级联的保护作用。成年Wistar大鼠在跑步机上跑步4周，然后使用改良的多平台方法急性睡眠剥夺24小时。睡眠剥夺后，将大鼠麻醉并在DG区域诱导L-LTP。在体内记录DG的细胞外场电位，并使用免疫印迹分析评估L-LTP表达前后L-LTP相关信号蛋白的水平。睡眠剥夺降低了海马体DG中磷酸化cAMP反应元件结合蛋白（P-CREB）以及其他上游调节因子（包括钙/钙调蛋白激酶IV（CaMKIV）和脑源性神经营养因子（BDNF））的基础水平。定期运动可防止睡眠剥夺动物中P-CREB和总CREB以及CaMKIV基础水平的受损。此外，定期运动可防止睡眠剥夺诱导的DG中L-LTP的抑制以及L-LTP后P-CREB和BDNF水平的下调。目前的研究结果表明，我们的运动方案可防止睡眠剥夺诱导的L-LTP缺陷以及关键信号分子的基础水平和刺激后水平。
