Leem Yea-Hyun, Chang Hyukki
J Exerc Nutrition Biochem. 2017 Dec 31;21(4):45-51. doi: 10.20463/jenb.2017.0033.
Chronic stress is a risk factor for behavioral deficits, including impaired memory processing and depression. Exercise is well known to have beneficial impacts on brain health.
Mice were forced to treadmill running (4-week) during chronic restraint stress (6h/21d), and then behavioral tests were conducted by Novel object recognition, forced swimming test: FST, sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti-Arc antibodies. Also, mice were treated with CX546 intraperitoneally during chronic restraint stress, and behavioral tests were assessed using Morris water maze, FST, and SI. Dissected brain was stained with anti-Arc antibody.
The current study demonstrated that chronic stress-induced impairment of memory consolidation and depression-like behaviors, along with the changes in calbindin-d28k and Arc protein levels in the hippocampal CA1 area, were attenuated by regular treadmill running. Further, prolonged ampakine treatment prevented chronic stress-evoked behavioral abnormalities and nuclear Arc levels in hippocampal CA1 neurons. Nuclear localization of Arc protein in hippocampal CA1 neurons, but not total levels, was correlated with behavioral outcome in chronically stressed mice in response to a regular exercise regimen.
These results suggest that nuclear levels of Arc are strongly associated with behavioral changes, and highlight the role of exercise acting through an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)-mediated mechanisms in a chronic stress-induced maladaptive condition.
慢性应激是行为缺陷的一个风险因素，包括记忆处理受损和抑郁。众所周知，运动对大脑健康有有益影响。
在慢性束缚应激（6小时/21天）期间，强迫小鼠进行跑步机跑步（4周），然后通过新物体识别、强迫游泳试验（FST）、社交试验（SI）进行行为测试。解剖后的大脑用抗钙结合蛋白-d28k和抗Arc抗体染色。此外，在慢性束缚应激期间，对小鼠进行腹腔注射CX546处理，并使用莫里斯水迷宫、FST和SI评估行为测试。解剖后的大脑用抗Arc抗体染色。
当前研究表明，慢性应激诱导的记忆巩固受损和抑郁样行为，以及海马CA1区钙结合蛋白-d28k和Arc蛋白水平的变化，通过定期跑步机跑步得以减轻。此外，延长安帕金治疗可预防慢性应激诱发的行为异常和海马CA1神经元中的核Arc水平。在慢性应激小鼠中，海马CA1神经元中Arc蛋白的核定位而非总水平与定期运动方案后的行为结果相关。
这些结果表明，Arc的核水平与行为变化密切相关，并突出了运动通过α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体（AMPAR）介导的机制在慢性应激诱导的适应不良状态中的作用。
